Transdermal cream containing immunomodulators and imiquimod

ABSTRACT

A method for creating a consolidated compound for delivering an immunomodulatory and imiquimod to a patient, comprising diluting immunomodulator extract to a desired dilution by transferring a desired quantity of the concentrated immunomodulator to an associated sterile container, the associated sterile container having a defined volume of diluted immunomodulator after dilution thereof, providing a viscous encapsulation material, selecting a prescribed amount of concentrated immunomodulator, the prescribed amount defined as that amount of the diluted immunomodulator extract required to provide a number of doses equal to the number of dispensable increments from the container containing the viscous encapsulation material, introducing the selected amount of each of the diluted immunomodulator extract into the viscous encapsulation material, introducing an amount of imiquimod into the viscous encapsulation material, and mixing the introduced amount of each of the diluted immunomodulator extracts and the introduced amount of imiquimod with the viscous encapsulating material.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/443,429, filed on Jan. 6, 2017, entitled TRANSDERMAL CREAM CONTAININGIMMUNOMODULATORS AND IMIQUIMOD (Atty. Dkt. No. RCMD-33332). Thisapplication also claims the benefit of U.S. Provisional Application No.62/443,390, filed on Jan. 6, 2017, entitled METHOD FOR DELIVERY OFIMMUNOMODULATORS AND IMIQUIMOD TO A PATIENT (Atty. Dkt. No. RCMD-33325).This application also claims the benefit of U.S. Provisional ApplicationNo. 62/443,433, filed Jan. 6, 2017, entitled METHOD FOR DELIVERY OF AMAINTENANCE DOSE OF IMMUNOMODULATORS TO A PATIENT (Atty. Dkt. No.RCMD-33333). This application also claims the benefit of U.S.Provisional Application No. 62/443,441, filed on Jan. 6, 2017, entitledMETHOD FOR DELIVERY OF A MAINTENANCE DOSE OF IMMUNOMODULATORS ANDIMIQUIMOD TO A PATIENT (Atty. Dkt. No. RCMD-33334). Application Nos.62/443,429, 62/443,390, 62/443,433, and 62/443,441 are hereinincorporated by reference in their entirety.

TECHNICAL FIELD

This application relates to the delivery of immunomodulators to apatient and, more particularly, to the use of carriers for thedispensing of such across the dermis of the patient.

BACKGROUND

Immunotherapy (IT) is recognized as most curative treatment forallergies. By exposing the immune system to slowly increasingconcentrations of immunomodulators such as an allergen or antigen, itwill eventually stabilize and regain control the portion that ishypersensitive to the allergen or antigen. In general, immunotherapy isthe “treatment of disease by inducing, enhancing, or suppressing animmune response.” Immunotherapies designed to elicit or amplify animmune response are classified as activation immunotherapies, whileimmunotherapies that reduce or suppress are classified as suppressionimmunotherapies. The active agents of immunotherapy are collectivelycalled immunomodulators. They are a diverse array of recombinant,synthetic and natural preparations, often cytokines.

Immunotherapy involved in the treatment of allergies is a type ofsuppression immunotherapy, often termed desensitization orhypo-sensitization. This is compared with allergy treatments such asantihistamines or corticosteroids which treat only the symptoms ofallergic disease. Immunotherapy is the only available treatment that canmodify the natural course of the allergic is, by reducing sensitivity tothe immunomodulators such as antigens or allergens. An antigen and anallergen and both cause one's immune system to respond. An allergen isan antigen, but not all antigens are allergens. An antigen is anysubstance that is capable of causing one's immune system to produceantibodies. They are typically organic, or living, produced proteins. Anallergen is any antigen that causes an allergic reaction. A non-allergenantigen could be a bacteria, virus, parasite, or fungus that causes aninfection. This could also be something else that causes antibody immunesystem response, like toxins, chemicals, tissue cells involved intransplants or blood cells from a blood transfusion. An allergen is anenvironmentally produced substance that causes an allergic reaction,although the substance may not be harmful. Allergens cause no reactionsin some individuals, while possibly causing a hypersensitive reaction inothers. Common allergens include such things as pollen, plants, smoke,feathers, perfumes, dust mites, toxic mold, food, drugs, animal dander,and insect bites and stings.

The exact mechanisms of how IT works are not fully understood, but theyinvolve shifting a patient's immune response from a predominantly“allergic” T-lymphocyte response to a “non-allergic” T-lymphocyteresponse.

Current accepted processes for performing allergy immunotherapy includeinjecting immunomodulators matter in the form of antigen material intopatient subjects. This is referred to as subcutaneous immunotherapy(SCIT), requiring a patient to visit a doctor's office for weeklyinjections. It's is very expensive and time-consuming. A secondtechnique, Sublingual immunotherapy (SLIT), involves the application ofallergy extracts (antigens), and allergens placed into a pill form andswallowed by the patient or disposed in “allergy drops” which are placedunder the tongue for the allergens/antigens to be absorbed into the oralmucosa. Transdermal patches may have been used without much success andmostly were used for patch testing to see if a patient reacts to variouschemicals or allergens.

Of the people who start traditional subcutaneous injected immunotherapy(SCIT), 90% fail to complete their therapy due to needle fatigue and notbeing able to see a doctor in their office once or more per week forseveral years. Further, doctors charge for every one of those visits.Further, doctors trained to give injections for allergy are concentratedin high population and upper middle class places. People in rural areasand people who do not live in upper middle class areas cannot get to anallergist for shots. Consider an inner city kid having to ride publictransportation and pay a high copay just to get a high risk injection ifan alternative therapy were available?!

Allergies are also linked to depression and suicide and are among thetop ten reasons for missed work and lost productivity. Lastly, allergiesand asthma result in billions of dollars in lost productivity andhealthcare costs among the 90% of allergy patients that either never getimmunotherapy or fail immunotherapy delivered under its currentadministration methods.

Immunotherapy basically involves a series of allergy shots given toreduce one's sensitivity to various allergens that may cause an allergicreaction. This immunotherapy can either be venom based orenvironmentally based. For venom based immunotherapy (VIT), treatmentsare available for allergies to stings such as honeybees, Yellowjackets,Hornets, paper wasps, fire ants and snakebites. For such things asinsect stings, very small amount of the insect venom is injected underthe skin in a dilute saline solution. This type of therapy isrecommended for all patients who have experienced systemic reaction toinsect sting and have specific IgE to venom allergens shown either myskin or blood test. Individuals with a history of a systemic reaction toan insect sting are at an increased risk of subsequent systemic stingreactions. VIT as compared to Environmental Immunotherapy is differentthan pollens and the such that one might be exposed to in theenvironment in that VIT is basically associated with allergens that areflown around inside a special injection device that, when counter, maythreaten the lives of those who are sent to it . . . Insect venomallergy or snake venom. The primary offenders associated with VIT areprone primarily insects that sting rather than those that might or, asnoted hereinabove, snakes. The insects that sting are typically membersof the order of Hymenoptera of the class insect. This can includemembers of the Vespid family, Yellowjackets, yellow Hornets, white-facedHornets and wasps. There also the class of Apids, including honeybeesand bumblebees. There's also the Formicid family that consists of fireants and Harvester ants.

To desensitize an individual against a particular venom, the process isto immunize the individual with small and graded doses of the venom.This is compared to the use of an anti-venom which is manufactured via apurified process in another animal such as a sheet. For example, theapproved anti-venom for the pit viper (rattlesnake, copperhead and watermoccasin) is based on a purified product made in sheet known as CroFab.These anti-venoms are typically administered through intravenoustechniques. However, there are some antivenoms for such things asstonefish and redback spider that are administered intramuscularly.These antivenoms are injected after a bite, as they are designed to bindto and neutralize the venom, halting further damage, but do not reversedamage already done. This is compared to desensitizing an individual bysmall graded doses.

In general, and antigen is any structural substance that serves as atarget for the receptors of an adaptive immune response or,alternatively, and more simply stated, and antigen is any substance thatcauses an immune system to produce antibodies against it. An allergen isa type of antigen that produces an abnormally vigorous immune responsein which the immune system fights off a perceived threat that wouldotherwise be harmless to the body. These reactions are termed allergies.Thus, by providing small graded doses of venom as the allergen, thiswould produce some type of immune response in the immune system thatwould generate anti-bodies to fight off the perceived threat. For smalldoses, the immune system can initially accommodate this and, as a dosesincrease, the immune system will continue to adapt and build upantibodies to this allergen, i.e., the venom of the particular insect orsnake or other such. These allergens associated with the venomimmunotherapy are specifically associated with allergens that originatefrom the internal organs of animals, insects or reptiles.

Currently, most allergens associated with venom immunotherapy are notreadily reimbursed when received from a pharmacist for the simple reasonthat the NDC code is not included in the database to which thepharmacist has access. Without an NDC code in the database, thepharmacist cannot access that information. By not being able to accessinformation, the pharmacist cannot interface with a benefits providerfor reimbursements nor can they have access to the Average WholesalePrice (AWP), which is the benchmark that has been used for many yearsfor pricing and reimbursement of prescription drugs for both governmentand private payers. Initially, this AWP was intended to represent theaverage price that wholesalers used to sell medications to providers,such as physicians, pharmacies, and other customers. However, the AWP isnot a true representation of actual market prices for either generic orbrand drug products. AWP has often been compared to the “list price” or“sticker price”, meaning it is an elevated drug price that is rarelywhat is actually paid. AWP is not a government-regulated figure, doesnot include buyer volume discounts or rebates often involved inprescription drug sales, and is subject to fraudulent manipulation bymanufacturers or even wholesalers. As such, the AWP, while usedthroughout the industry, is a controversial pricing benchmark.

The AWP may be determined by several different methods. The drugmanufacturer may report the AWP to the individual publisher of drugpricing data, such as Medi-Span. The AWP may also be calculated by thepublisher based upon a mark-up specified by the manufacturer that isapplied to the wholesale acquisition cost (WAC) or direct price (DIRP).The WAC is the manufacturer's list price of the drug when sold to thewholesaler, while the DIRP is the manufacturer's list price when sold tonon-wholesalers. Typically a 20% mark-up is applied to themanufacturer-supplied WAC or DIRP, which results in the AWP figure.

The publishers then in turn sell these published AWPs to government,private insurance, and other buyers of prescription drugs, who use thesedata tables to determine reimbursement and retail prices. Because AWP isa component of the formulas used to determine reimbursement, elevatedAWP numbers can drastically increase the dollar amount that government,private insurance programs, and consumers with coinsurance must pay.

Pharmacies typically buy drugs from a wholesaler and then sell them tothe public. Many patients have coinsurance or copayments, where theyonly pay for a portion of their prescription cost. The insurance companythen pays the rest of the cost (the reimbursement) to the pharmacy.Insurance companies include prescription benefit manager (PBM), healthmaintenance organization (HMO) or government programs, such as Medicaidor Medicare Part B or D. In addition, the pharmacy receives a dispensingfee for filling the prescription. Fees are, for example, set between $3to $5 per prescription, but may vary by state.

Reimbursements are based on AWPs. However, pharmacies purchase drugsbased on the WAC. The difference between the WAC (what the pharmacyactually paid for the drug) and the reimbursement from insurance (basedon AWP) is known as the spread, and equates to the profit that thepharmacy receives.

Market pricing on brand drugs tend to be about 16.6 percent less thanthe AWP. However, the relation of AWP to generic pricing is not clear.Older generics tend to have a large spread between the AWP and WAC,which in turn gives a large spread, and higher profit margins for thepharmacy or other provider of the drug. Many payers, such as PBMS orHMOs, will determine a maximum allowable cost (MAC) pricing on genericsto avoid being overcharged. Newer generic products, compared to oldergenerics, may not have as favorable of a spread, thus the need for MAC.

Collusion between AWP publishers and wholesalers to artificially inflatethe AWP, and in turn increase the spread, has led to court cases in theU.S. In these cases, it was alleged that increasing the spread benefitedthe wholesaler because customers (pharmacies and large institutions)were more likely to buy from them than a competing wholesaler where thespread was not as desirable. The publisher of AWPs profited becausepharmacies were more likely to buy the pricing lists from the publisherthat noted the higher AWPs used in calculating the spread, than to buythem from other publishers with lower AWPs. Due to this pricing fraud,many payers, including government payers, are no longer using AWP forpricing, and are switching to other more transparent pricing benchmarks,such as WAC or AMP (average manufacturers price). However, AWP may stillbe found in use in the U.S. because it has been the standard fordecades.

However, in order for a pharmacist to access the AWP and to be able tointerface with benefits providers, the product associated with an NDCmust be in the database. Currently, nonvenoms are an item that does notexist in the database.

SUMMARY

A method for creating a consolidated compound for delivering animmunomodulatory and imiquimod to a patient is provided. The methodcomprises the steps of providing a plurality of containers ofconcentrated immunomodulator extract, for each container of concentratedimmunomodulator extract, diluting the immunomodulator extract with apredetermined dilutant in an associated sterile container approved forsuch dilution and to a desired dilution by transferring a desiredquantity of the concentrated immunomodulator to the associated sterilecontainer, the associated sterile container having a defined volume ofdiluted immunomodulator after dilution thereof, such that there is anassociated sterile container for each container of concentratedimmunomodulator extract, providing a viscous encapsulation material thatis able to carry immunomodulators across the dermis of a patient andhaving a defined volume disposed within a container, the defined volumedivided into a plurality of dispensable increments, selecting aprescribed amount from each of the sterile containers associated witheach of the containers of concentrated immunomodulator, the prescribedamount for each of the sterile containers defined as that amount of thediluted immunomodulator extract required to provide a number of dosesequal to the number of dispensable increments from the containercontaining the viscous encapsulation material, a dose providing adesired therapeutic effect to a patient for each of the dilutedimmunomodulator extracts, introducing the selected amount of each of thediluted immunomodulator extract into the viscous encapsulation material,introducing an amount of imiquimod into the viscous encapsulationmaterial, and mixing the introduced amount of each of the dilutedimmunomodulator extracts and the introduced amount of imiquimod with theviscous encapsulating material in which it was introduced.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding, reference is now made to thefollowing description taken in conjunction with the accompanyingDrawings in which:

FIG. 1 illustrates a diagrammatic view of a dilution sequence ofdiluting a concentrated antigen extract;

FIG. 2 illustrates step of mixing imiquimod and a dose of dilutedantigen into a container of transdermal cream;

FIG. 3 illustrates a delivery device for delivering specified doses;

FIG. 4 illustrates a process flow for diluting an antigen extract;

FIG. 5 illustrates a process flow for mixing imiquimod and dilutedantigen with a transdermal cream;

FIG. 6 illustrates a process flow of the application of antigen via thetransdermal cream;

FIG. 7 illustrates a process flow for the overall distribution chain;

FIG. 8 illustrates a process flow for multiple extracts;

FIG. 9 illustrates an alternate embodiment of FIG. 8;

FIG. 10 illustrates a flowchart depicting the operation of a physicianevaluating a patient to determine an overall desensitization allergyprogram;

FIG. 11 illustrates a flowchart depicting the operation of a compoundpharmacist providing to the physician all of the allergens at thespecific dose for a given program for a given patient;

FIG. 12 illustrates one embodiment of a specific operation of creatingthe dilution sets in flowchart form;

FIG. 13 illustrates a diagrammatic view of one embodiment of adispensing operation for assembling the overall individual dosages orcombined dosages in a single package group for delivery to a physician;

FIG. 14 illustrates one embodiment of a specific operation of creatingthe dilution sets in flowchart form;

FIG. 15 illustrates a diagrammatic view of one embodiment of adispensing operation for assembling the overall individual dosages orcombined dosages in a single package group for delivery to a physician;

FIG. 16 illustrates an overall therapeutic program flow for treating apatient after a total program with associated dilution sets has beendefined;

FIG. 17 illustrates a general diagrammatic view of the overall interfaceof basic databases;

FIG. 17A illustrates an NDA code;

FIG. 18 illustrates a diagrammatic view of a database that is populatedby a central control system;

FIG. 19 illustrates a flow chart for the operation at the centralcontrol system for receiving NDCs from the manufacturer;

FIG. 20 illustrates a flow chart for the operation of populatingthird-party database by the central control system;

FIG. 21 illustrates a flow chart for the operation at the pharmaceuticallocation;

FIG. 22 illustrates a flow chart for the overall generation of the AWPand the interface with the benefit providers;

FIG. 23 illustrates a diagrammatic view of flow beginning at the pricktest and following through to filling the prescription at the pharmacistlocation;

FIG. 24 illustrates a flowchart for interfacing with database foraccessing benefits by the pharmacist;

FIG. 25 illustrates a flowchart for the parsing operation at thedatabase for parsing non-NDC allergens to an NDC-bearing baseconcentrated allergen;

FIG. 26 illustrates a flowchart for one example of processing aphysician script;

FIG. 27 illustrates a diagrammatic view of a table in a relationaldatabase relating distributed doses back to NDC-bearing dose;

FIG. 27A illustrates a diagrammatic view of a table showing the dilutionprocedure;

FIG. 28 illustrates a second example of that illustrated in FIG. 26;

FIG. 29 illustrates a diagrammatic view of processing of a scriptreceived from a physician at a pharmacist to compound a patient-specificdosage;

FIG. 30 illustrates an alternate embodiment of that illustrated in FIG.29;

FIG. 31A illustrates a diagrammatic view of a process of filling ascript received from a position and FIG. 31B illustrates a tableassociated with such process;

FIG. 32 illustrates an overall process flow illustrating the prick test,the script flowing through to the final patient does;

FIG. 33A illustrates a flowchart for parsing an antigen having a basedose with more than the prescribed antigens and FIG. 33B illustrates atable associated with the parsing operation;

FIG. 34A illustrates a top view of one embodiment of antigen transdermalpatch sheets;

FIG. 34B illustrates a cross-sectional view of one embodiment of anantigen transdermal patch;

FIG. 35A illustrates a perspective view of one embodiment of amulti-antigen patch;

FIG. 35B illustrates a cross-sectional view of one embodiment of amulti-antigen patch;

FIG. 35C illustrates a perspective view of one embodiment of amulti-antigen patch;

FIG. 35D illustrates a cross-sectional view of one embodiment of amulti-antigen patch;

FIG. 35E illustrates a perspective view of one embodiment of amulti-antigen patch;

FIG. 35F illustrates a cross-sectional view of one embodiment of amulti-antigen patch;

FIG. 36 illustrates one embodiment of a process for providing a singledose of antigen at a prescribed level in an antigen carrier;

FIG. 37A illustrates a perspective view of one embodiment of amulti-antigen patch;

FIG. 37B illustrates a cross-sectional view of one embodiment of amulti-antigen patch;

FIG. 37C illustrates a cross-sectional view of one embodiment of amulti-antigen patch after a liner is removed;

FIG. 37D and FIG. 37E illustrate a cross-section view of one embodimentof applying a peelable release liner to a multi-antigen patch;

FIG. 38 illustrates one embodiment of a multi-antigen selectionoperation;

FIG. 39A illustrates a cross-sectional view of one embodiment of amulti-antigen patch;

FIG. 39B illustrates a top view of one embodiment of a multi-antigenpatch;

FIG. 39C illustrates a top view of one embodiment of a multi-antigenpatch after a liner is removed; and

FIG. 39D and FIG. 39E illustrate a cross-section view of one embodimentof applying a peelable release liner to a multi-antigen patch.

DETAILED DESCRIPTION

Referring now to the drawings, wherein like reference numbers are usedherein to designate like elements throughout, the various views andembodiments of an individually customized allergy cream for individualpatient profile are illustrated and described, and other possibleembodiments are described. The figures are not necessarily drawn toscale, and in some instances the drawings have been exaggerated and/orsimplified in places for illustrative purposes only. One of ordinaryskill in the art will appreciate the many possible applications andvariations based on the following examples of possible embodiments.

The principles of the present disclosed embodiment include a processthat involves the use of transdermal carrier creams infused withantigens that can be applied to the patient's skin surface. Further, theantigens can also be carried across the dermal layer along withantihistamines, anti-inflammatory medications, imiquimod, and steroidsas well as other drugs that may prevent a severe allergic reaction inpatients and thus possibly avoid life-threatening anaphylacticreactions. The antigens can also be carried to various depths based uponthe physician's requirements. Some transdermal carrier creams penetratejust beyond the deepest skin layer where many of the human cells thatrecognize antigens as foreign invaders reside. If the physician wishesto treat the patient in a more traditional manner, some transdermalcarrier creams can penetrate the patient well below the skin and reachareas of high vascularity thus pushing the antigens into the bloodstream much the same as utilizing a hypodermic needle.

The transdermal carrier creams can be used to carry only antigens intothe body or they can be used in conjunction with antigens and othermedications that can be carried across the skin as combination therapiesfor allergies.

Referring now to FIG. 1, there is illustrated a depiction of a techniquefor diluting immunomodulators such as antigens, as one example.Preparation of a diluted antigen is performed first by receiving abottle of extract concentrates from an approved vendor. These areformulated in a given weight/volume (w/v) format with a given antigenassociated therewith. For typical antigens such as those associated withthe cat antigen, these are relatively well controlled. Typically, avendor will provide an extract for a single antigen or allergen.Allergens such as pollen and the such are not as well controlled due tothe technique for collecting such. In any event, there are typicallyvery few approved vendors for these extracts and allergist typicallyreceives these vendor provided concentrates in a sufficient quantity tomake the necessary diluted solution.

Allergen extract is typically comprised of a non-allergenic material, anon-allergenic protein and an allergenic protein. The extractionsolutions can be aqueous containing saline and phenol work could be aglycerinated solution. The allergen is added, the units of measure aresometimes referred to as “AU” for “allergy units,” typically used formites. These are referred to as “AU/mL.” For such things as grass andcat, the term “BAU” is used for “bioequivalent units.” For otherallergens, the terminology is, for example, 1:20 w/v, which stands for 1g source material per 20 mL of fluid. The relationship between BAU and1:20 w/v depends upon the extract. In any event, there is a definedamount of extract contained within the concentrate.

When concentrated extracts are formulated by an authorized vendor, theyare typically provided in standardized versions and non-standardizedversions. In standardized versions, they typically are provided in a 50%glycerin dilutant. They can either be a single allergen extract or theycan be a mix. For example, one can obtain a “9 Southern Grass Mix(concentrate)” which contains equal parts of: 2 Bermuda at 10,000BAU/mL, P27 7 Grass at 100,000 BAU/mL, 15 Johnson at 1:20 w/v. Fornon-standardized extracts, these are typically provided in either aglycerin dilutant or an aqueous dilutant such as saline. They can be asingle extract or a mix. Thus, whenever a concentrated extract isreferred to hereinbelow, this refers to a formulation that is providedby an authorized vendor that can be diluted in accordance with theprocesses described hereinbelow. These are typically provided in the 50mL bottles with a needle compatible.

Referring back to FIG. 1, the extract concentrate is disposed in abottle 102. This is a sterile concentrate that has an injectionstoppered top 104. There are provided a plurality of five 5 mL sterileinjection stoppered bottles 106, 108, 110, 112 and 114, although therecould be more and the bottles or containers could be larger than 5 mL.Each of these bottles has disposed therein a defined amount of dilutant,depending upon what the final required to be. Typically, the amount ofdilutant is 4.5 mL. The procedure is to, first, extract a defined amountof the concentrated extract from the bottle 102 and dispose it in thebottle 106. This is facilitated by the sterile hypodermic that isinserted through the stopper at the top of the bottle 102 to extractconcentrate and then the hypodermic is inserted to the stopper in thebottle 106 to inject extract from bottle 102 into bottle 106. Typically,the concentration in the concentrated extract bottle 102 is 1:20 w/v.This will result in a dilution of 1:10 in bottle 106. If the amountinjected is 0.45 mL. Then, 0.45 mL of the diluted solution from bottle106 is then extracted and inserted into bottle 108, resulting in a 1:100dilution of the original concentrate in model 108. The process isrepeated up to the bottle 114 to provide a solution that is at adilution of 1:100,000 of the original concentrate. This is aconventional way to provide a selected dilution of the original antigen.However, it should be understood that any concentration level can beprovided from one bottle to the next. Purpose of using the sequentialbottles is to allow an achievable portion of one bottle to bedistributed to the next bottle, rather than trying to extract a verysmall amount of the initial concentrated extract. Typically, anallergist will then extract from the desired dilution an amount of thediluted antigen for injection percutaneously. Typically, desensitizationis achieved by using the most diluted antigen level initially andsequentially moving up to a higher concentration level over time 1.

Illustrated in FIG. 1 are three hypodermic needles, one selecting a“dose” from bottle 114, and labeled hypodermic 116, a second hypodermicneedle 118 for retrieving a dose from bottle 112, a third hypodermicneedle 120 for extracting a dose from bottle 110. Each of the hypodermicneedles 116, 118 and 120 will contain a different diluted dose. Thesewould typically be separate needles in the event that the allergist ormedical professional is injecting a patient. For other purposes, theycould be the same needle, depending upon the dose or concentrationrequired. A “dose” is defined the amount all the diluted product thatwould be required for the desired immunotherapy. This is defined by themedical professional. If, for example, bottle 112 were utilized, it maybe that 1 mL of diluted solution constituted a “dose.” It could be thatless than 1 mL constituted an “dose.”

Referring now to FIG. 2, there is illustrated a diagrammatic view ofinjecting a dose into a container 202 which contains a quantity oftransdermal cream 204, which transdermal cream is a viscousencapsulation material for containing this dose in an emulsion. Thetransdermal cream may also have injected and mixed therein a quantity ofimiquimod. Imiquimod is a medication, usually given within a cream at aparticular concentration (often 5% by weight, but formulations may varybetween 0.5% to 9%) that acts as an immune response modifier, whichserves to increase the activity of the body's immune system. U.S. Pat.Nos. 5,238,944 and 5,736,553 to Wick et al., which are hereinincorporated by reference in their entirety, describe certain imiquimodcompositions. One such cream composition is as follows:

TABLE 1 % by Weight Oil Phase1-Isobutyl-1H-imidazo[4,5-c]-quinolin-4-amine 5.0 Isostearic acid 25.0Benzyl alcohol 2.0 Cetyl alcohol 2.2 Stearyl alcohol 3.1 Petrolatum 3.0Polysorbate 60 3.4 Sorbitan monostearate 0.6 Stearic acid — AqueousPhase Glycerin 2.0 Methylparaben 0.2 Propylparaben 0.02 Purified water53.48It will be understood, however, that other formulations, such as otherformulations disclosed in U.S. Pat. Nos. 5,238,944 and 5,736,553 to Wicket al., may be used.

Imiquimod signals to the innate arm of the immune system through thetoll-like receptor 7 (TLR7), which is commonly involved in pathogenrecognition. Cells activated by imiquimod secrete cytokines. There isalso evidence that application of imiquimod to the skin can lead to theactivation of Langerhans cells, which migrate to the local lymph nodesto activate the adaptive immune system. Other cell types activated byimiquimod include natural killer cells (a type of cytotoxic lymphocyte),macrophages, and B-lymphocytes. All of this combined contributes to thestrong antitumoral activity of the compound. Imiquimod has historicallybeen used to assist in the treatment of skin conditions such as warts,genital warts, superficial basal cell carcinoma, and actinic keratosis.A particular formulation of imiquimod is C₁₄H₁₆N₄, but otherformulations exist and may be used.

A container 210 containing imiquimod may be provided. A dropper 212 maybe used to collect the imiquimod from the container 210. It will beunderstood that the dropper 212 is only illustrative of one way tocollect the imiquimod from the container 210 and any other way ofcollecting and measuring the amount collected may be used. The amountcollected may be the amount needed for a single dose of imiquimodappropriate for the patient. A typical dose of imiquimod may be 250 mgwhen already in a cream, or an amount that can be applied to 25 squarecentimeters of skin. The amount of imiquimod collected may also be anamount for providing the desired amount imiquimod proportional to theamount of transdermal cream needed. For example, an amount of imiquimodthat will comprise 5% by weight of the transdermal cream 204 may becollected. The dropper 212 is then used to inject the imiquimod into thecontainer 202 and into the transdermal cream 204.

A hypodermic needle 206 is also illustrated which contains a single doseor multiple doses of diluted antigen as noted hereinabove, the lastbottle 114 will have 5 mL of diluted antigen disposed therein. If theallergist determines that a dose is 1 mL, then a single dose could bedisposed in the quantity of transdermal cream 204. If the allergist ormedical professional determined that the container 202 should containthree doses, 3 mL would be selected and disposed within the container202. It is noted that one limitation of the bottle 114 for the 1:100,000dilution level or the bottle 112 for the 1:10,000 dilution level eachhas a finite volume. Since the finite volume is, in this example, 5 mL,and if the dose is determined to be 1 mL, then only 5 doses could beprovided for a getting a given dilution process. Thus, only a maximum offive doses could be disposed within the container 202. Once theimiquimod and the diluted solution of the immunomodulators in the formof an antigen is injected into the transdermal cream 204, it issubjected to a mixing operation via a mixer 208. In other embodiments,the imiquimod may be injected into the transdermal cream 204 and mixedbefore the diluted antigen is mixed into the transdermal cream 204, orvice versa.

A transdermal cream is basically a viscous encapsulation material thatincludes a base that is provided to transport drugs through the skin.There are some types of transdermal bases or creams that allow fordelivery of up to four drugs or compounds through the skinsimultaneously. The creams are different than transdermal patches inthat they are rubbed on a particular area of the skin and are absorbedthrough the skin in a very short period of time and are well suited tosmall molecule antigens. One such transdermal cream is that manufacturedby PCCA under the trademark Lipoderm®. This base is utilized for thepercutaneous absorption of drugs through the skin. As such, not only canantigens be provided in a particular dose within the transdermal cream,but other drugs such as antihistamines, imiquimod, and pain medicationscan also be provided, depending upon the particular needs of a patient.The desire for the immunomodulators in the form of antigens is that theybe disposed within the subcutaneous region just beneath skin or thestratum corneum, which is the outermost layer of the epidermis. Thislayer, of course, very thin thickness throughout the body. The desire isto allow, via the transdermal cream, the transport of theimmunomodulators through this stratum corneum to the subcutaneous tissueor the hypodermis.

Referring now to FIG. 3, there is illustrated a diagrammatic drawing ofa distribution pump 303 that has a container 305 and a pump head 307associated therewith. Disposed within the interior of the container 305is a quantity of transdermal cream that represents four doses of theantigen at the desired dilutant level and imiquimod. Thus, for example,the last bottle 114, as depicted in FIG. 1, would have around 5 mL ofdiluted antigen disposed therein. If the desired dosage for the patientwas 1 mL, then 4 mL would be extracted from the bottle 114 to provide 4doses and disposed within a sufficient amount of transdermal cream torise to a level 310 within the container 305. The dosage increment isthat represented by at least one full pump stroke or a defined number ofpump strokes. For example, the directions might state that a single fullpump stroke represented a single dose and that was what was to beapplied at a particular time in accordance with the directions of amedical professional. It might be that multiple strokes are required perdose. In that case, the directions would indicate that the dose is to beapplied would require that number of pump strokes. All that would berequired would be to know the amount of transdermal cream that wasrequired to fill the container 305 to the level 310 and then inject fordosages therein and mix the material. The transdermal cream could be atransdermal cream that already had a predetermined amount of othermedications contained therein such as antihistamines, imiquimod, and/orpain medication.

In addition, a sealed straw type tube could be used instead of themetered pump. In this type of delivery device, a premeasured amount ofthe viscous material, i.e., the transdermal cream, can be provided thatcould represent, for example, a single dose. However, as describedhereinbelow, the amount of cream for this single dose represents avolume of cream that contains, in one example, a single diluted dose ofa single concentrated extract or, alternatively, a single dose each ofmultiple concentrated extracts. For the latter, all that is required isthat the volume of the transdermal cream first be defined and then thesingle dose of each of the concentrated extracts disposed therein.

The transdermal cream or carrier is, as described above, a viscousencapsulation material for encapsulating a finite amount ofimmunomodulators or antigen therein. This transdermal cream is basicallya consolidator. As such, more than a single immunomodulator can bedisposed within the cream of. This, of course, depends upon what thesmallest increment of dosage is comprised of. If, for example, thecontainer 202 in FIG. 2 contained 30 g of encapsulation material and itwas possible to extract a single gram per application, this would meanthat 30 doses of the immunomodulator would have to be injected ordisposed within the encapsulation material, i.e., the transdermal cream.To facilitate this, the dilution must be at the appropriate level. If,for example, 3 mL of diluted immunomodulator were added to the 30 g ofviscous encapsulation material, then 0.3 mL of the dilutedimmunomodulator would constitute a single dose. In that example, supposethat the allergist or medical professional determined that this was thecase and required five separate immunomodulators to be disposed withinthe viscous encapsulation material. This would then require theconsolidator to basically add 3 mL of diluted immunomodulators from thedesired vial or bottle having the desired dilution of the desiredimmunomodulators or antigen. For this example, this would require threeinjections, each being 3 mL. The actual increase in the volume of theviscous encapsulation material disposed within the container, containing30 g of viscous encapsulation material would only be slightly greaterthan that value. If the distribution mechanism were able to distribute asingle grand of viscous encapsulation material as a single “dose” of thematerial, this would actually provide a single dose of five differentantigens in a single application of 1 g of the material onto the skin.In the example of FIG. 3, this would require, for each volume of eightdose of viscous encapsulation material, that the appropriate amount ofimmunomodulators or antigen be disposed therein.

Referring now to FIG. 4, there is illustrated a process flow for theembodiment of FIG. 1. This is initiated at a process block 402 and thenproceeds to block 404 wherein a certain amount of concentrated extractis received from a vendor, this being a qualified or authorized vendorfor the extract. This is typically at a predetermined concentrate levelof, for example, 1:20 m/v. The process then flows to a block 408 whereina defined quantity of, for example, 0.45 mL is transferred to a 5 mLbottle which already has a quantity of 4.5 mL buffered saline solutiondisposed therein. The process then flows to a block 410 to determine ifthis was the last dilution step needed, as described hereinabove,depending upon what level of dilution is necessary. If, for example, bysteps of dilution are required for a particular patient, and all fivesteps would be processed. However, it is not necessary to do all fivesteps if an intermediate dilution is required. This essentiallycustomizes the overall operation for a particular patient. Further, theindustry is so regulated such that only 5 mL bottles can be utilized forthis dilution process. Thus, it will only be a maximum of 5 mL ofdiluted material available at any step prior to proceeding to the nextstep. Thus, if all 5 mL are required, then the next step is not desiredor useful. If it is not the last dilution step, the process flows to ablock 412 to extract 0.45 mL of diluted antigen from the current 5 mLbottle and then flows back to the input of the process block 408 afterincrementing the bottle count. This continues until the last dilution,at which time the process flows from the block 410 to a terminate block416.

Referring now to FIG. 5, there is illustrated a process flow forcombining the selected diluted antigen with the viscous encapsulationmaterial or transdermal cream, which is initiated at a block 502 andproceeds to a process block 504 to select the diluted antigen bottle orbottles from which to extract the dose or doses. At a process block 506,the prescribed number of doses is extracted from that particular bottle,keeping in mind that only a maximum of 5 mL of the diluted antigen isavailable. At the process block 508, the selected number of doses of thediluted antigen is injected into a predetermined quantity of transdermalcream from one bottle for a single antigen mixture and from multiplebottles for a multiple antigen mixture. At step 509, imiquimod isinjected into the transdermal cream at a desired amount. The transdermalcream may also already contain other medications, such as imiquimod, orthose other medications may be mixed into the transdermal cream at alater time. The process then flows to block 510 to mix the injectedcream. The process then flows to a block 512 to dispose the mixedtransdermal cream in a dispenser bottle such that a discreet amount oftransdermal cream can be dispensed so as to extract a single dose of thediluted antigen contained therein.

Referring now to FIG. 6, there is illustrated a process flow for theapplication of the transdermal cream. This is initiated at a processblock 602 and then the flow proceeds to process block 604. Thetransdermal cream is dispensed in a single quantity that corresponds toa single dose at the specified antigen dose. This instruction isprovided by a medical professional and, if followed, is substantiallyidentical to the subcutaneous injection of the same dose directly fromthe hypodermic needle. Once dispensed, this amount of transdermal creamis applied to the skin by the patient or a medical professional, asindicated by a process block 606.

As an example, suppose that the container provided to the patientcontained in 30 g of viscous encapsulation material or transdermalcream. In this material was contained a plurality of doses such that asingle dose is contained within 1 g of material. The physician mightprovide a schedule or regimen that, in the first week requires one doseto be applied on Monday, Wednesday and Friday of that week. This wouldrequire the patient to dispense a single gram of material on each ofthose days constituting a single dose for each of those days and applyit. In the next week, the regimen is to apply two doses three times aweek on Monday, Wednesday and Friday, requiring the patient to dispense2 g of material for each of those dates. In the third week, the regimenmight require three doses to be applied three times in that week onMonday, Wednesday and Friday. This requires the patient to dispense 3 gof material for each of those days and apply it. In the fourth week, theregimen might require the patient to dispose four doses of the materialonto the skin on three days of the week, Monday, Wednesday and Friday.This would require the patient to dispense 4 g of material for each ofthose three days and apply it.

The application transdermal cream could be to any portion of the skin,but preferably, it would be to an area that represents an area of sometype of allergic reaction. If for example, the patient experiences sometype of rash on their neck, they would apply the mixture to that area ofthe body. If not, it could be applied only to the arm.

Referring now to FIG. 7, there is illustrated in overall flow of theoperation of moving concentrated antigen from a vendor to an end user.As noted hereinabove, the liquid antigen in a concentrated extract wasfirst received from a vendor, which is basically a combination of asingle antigen or antigens suspended in a sterile agent. This isindicated by a block 702. The antigen is then diluted from this extractto a desired diluted level, as indicated by a process block 704. This iscombined in a block 706 with a sterile viscous encapsulation andcontainment material, i.e., a transdermal cream, for distribution. This,as described hereinabove, will typically be a defined number of doses ofa single diluted antigen or multiple diluted antigens, wherein a dose isagain defined as being a typical dose that a medical professional wouldadminister to a patient in an office visit necessary to achieve atherapeutic result. This is either transferred as a combined antigen(diluted)/encapsulation product for storage on a shelf, as indicated bya block 712, or it would be transferred to a medical professional formanagement and disposition.

Referring now to FIG. 8, there is illustrated a diagrammatic view ofthree different extracts of antigens/allergens 802, 804 and 806. Each ofthese is for a particular antigen or allergen. The first two are forantigens respectively associated with a cat and a dog. The third is foran allergen associated with pollen. They are each diluted in accordancewith the process described hereinabove with respect to FIG. 1. Asillustrated, the antigen extract in bottle 802 is transferred as adiluted level to either an encapsulation material in a container 810 or812, each at a different diluted level. This is similarly the case withrespect to the antigen in bottle 804 and the allergen in 806 wherein thediluted level of the antigen in the bottle 804 is disposed in containers814 and 816 and the diluted level of the allergen in bottle 806 isdisposed in containers 818 and 820. Typically, any extract will be 100%pure with respect to the particular extract. These concentrated extractsare not typically mixed, which is typically a function that the medicalprofessional will perform. This, of course, is a customized mixture fora particular patient. For storage on the shelf, the operation of FIG. 8will be facilitated in order to ensure that the containers 810-820contained only a single antigen. Thus, when transferring the containerto a store, for example, this would be stored on the shelf as a singleallergen combination. This is for a situation where in a single bottleor container of the viscous encapsulation material or transdermal creamwould be associated with only a single immunomodulator or antigen.

Referring now to FIG. 9, there is illustrated an alternate disclosure tothat of the embodiment of FIG. 8. In this embodiment, each of theimmunomodulators or antigens at the concentrated levels in the bottles802-806 are diluted in accordance with the process noted hereinabovewherein they are sequentially diluted in the associated 5 mL bottles.However, note that only a maximum of 5 mL can be extracted from a givenbottle at the last dilution level. If, in this example, it is desired todistribute a predefined number of doses to a final carrier 902 having 30g of viscous encapsulation material or transdermal cream and imiquimoddisposed therein and each dose will be associated with a single gram ofthat material, then the amount of diluted antigen must be adjusted suchthat single dose is contained within 0.3 mL of the material. Thereafter,if 3 mL of antigen is extracted from a given bottle, this constitutes 30doses such that a single dose will be associated with a single gram ofthe final encapsulation material. In this example, from each of the lastdilution bottles for each of the concentrate bottles 802-804, 3 mL inextracted and inserted within the container 902 containing 30 g ofmaterial. Thus, for each gram of material, there will be a single doseof the particular antigen associated there with. Thus, encapsulationmaterial in the container 902 now acts as a consolidator of all of theantigens. It is noted that, if the starting material is, for example, 30g, and there is provided a dispenser capable of dispensing a single gramof material at a time, the addition of the antigens might increase thevolume slightly. This, of course, depends upon what the volume of creamconstitutes for a gram of cream for the viscous encapsulation material.This may increase the overall quantity or volume by a small percentage,but, in general, the overall volume is not increased. If, for example, alarge number of antigens were introduced into the viscous material 902in this matter, the initial volume of the viscous material magnitudecould be decreased to account for such, yielding a total containerhaving 30 g disposed therein which is comprised of the viscousencapsulation material and all of the particular antigens orimmunomodulators desired.

As a distribution mechanism, all that is necessary is for theconsolidator to have available a kit with the appropriate dilutionbottles and the concentrated extract for each concentrated extractdesired. The amount of material from one bottle to the next is thendefined such that the consolidator can accurately control the amount ofdiluted antigen that is in the last bottle. This would then allow theconsolidator to create the container 902 containing the appropriateamount of doses of antigens therein. Since a particular kit may have asingle bottle of concentrated extract therein, there may be multipledilution bottles provided to allow more than one final dilution toprovide another consolidated mixture of transdermal cream with adifferent combination of antigens.

Allergies are the leading cause of asthma and asthma is a debilitating,life threatening, disease. It costs millions of dollars to treat.Allergy immunotherapy is the only known treatment for the prevention ofasthma and further is the only treatment that may possibly reverse thedisease. The topical antigen allergy treatments will likely affect 90%of allergy and asthma patients.

Referring now to FIG. 10, there is illustrated a flowchart depicting theoverall operation of a physician providing a therapeutic program to apatient. In this operation, a physician is able to evaluate the allergenneeds of a particular patient and prescribe a particular program forthat patient and effectively implement such program. The operation inFIG. 10 is initiated at a block 1010 and proceeds to a function block1012, wherein a patient enters into a consultation with a physician forthe purpose of determining sensitivities to certain allergens. In ablock 1014, the physician orders various tests to determinesensitivities of a particular patient to one of multiple allergens. Thiscan be facilitated through a prick test, through a DNA test, through ablood test, or any other technique for determining sensitivities toparticular allergens. The physician typically runs the tests at theiroffice and can determine from, for example, a prick test, thesensitivities on a relatively expedient basis. In some embodiments, thetest may be analyzed by the physician, as indicated by a block 1016. Ofcourse, the particular lab that provides the results may also provide ananalysis therewith. Similarly, the entire testing process can beout-sourced to another lab or testing facility.

After the results have been analyzed, the program proceeds to a block1018 wherein the physician designs a therapeutic program based on theresults. This therapeutic program determines the particular allergens towhich a patient is sensitive, which determined allergens will definewhat allergens must be used for desensitization. The program typicallyinvolves first introducing subcutaneously a small dosage of the actualallergen or allergens to which the patient is sensitive. This can bedone on an allergen-by-allergen basis or, preferably, multiple allergenscan be introduced at the same time. Typically, the first dose is a smalldose that is introduced multiple times over the course of a predefinedperiod of time. At the end of this first time, a second and higher doseof the allergen or allergens is introduced over a second time period atdefined increments of introduction. Each introduction of the allergen isdefined as a “dose.” This overall process continues until a sixth doselevel is provided, this being the maintenance dose. This particularmaintenance dose is the highest dose that an individual is expected totolerate. Any higher of a dose may not be beneficial overall and mayprovide some harmful effects to the patient.

Once the program has been designed for a particular patient, i.e., theparticular allergens that are necessary for the defined program and theparticular dosages, a script is then written for the program to bedelivered to a compound pharmacist. This is indicated at a block 1020.This is then sent to the compound pharmacist, as indicated by block1022. In general, the physician is trained to understand for aparticular patient, i.e., by sex, age, weight, etc. or just generalmedical condition, a particular starting dose for particular allergensor combinations thereof. The physician will be provided with charts andthe such to determine what allergens can be combined in a singleintroduction dose as a single allergen or as a combination with otherallergens. Once the initial dose is defined, standard operatingprocedure defines the increasing doses therefrom. Thus, once thephysician defines the initial dose, it can then be assured that all theremaining dosages at the higher concentration levels will be consistent.Further, once the program is designed, it is designed such that all ofthe allergens are extracted from the same batch. If, alternatively, thephysician were to order the first set of doses at the firstconcentration level for the first period of time at a different timethan the last concentration level for the last maintenance dose, it ispossible that they would be extracted from a different batch which wouldhave different concentrations and the such. If it is all derived fromthe same initial batch, the desensitization from one concentration levelto another can be fairly well guaranteed and provide the physician witha relatively high degree of confidence in the escalating concentrationsbetween doses in different periods of time.

Referring now to FIG. 11, there is illustrated a flowchart depicting theoperation at the compound pharmacist. The program is initiated at ablock 1102 and then proceeds to a decision block 1104 to determine if ascript has been received for a particular patient from a physician. Thisscript will indicate to the compound pharmacist the overall program forallergen desensitization. The program flows to a block 1106 to create alog for that patient and into a function block 1108 to select thevarious concentrations as the basic concentration for each allergen orallergens that is specified by the script. It may be that, for example,a physician has determined that the patient is allergic to dog, cat andhay. The compound pharmacist would then select a file for each of theseallergens which would be at a base concentration level, as describedhereinabove with respect to FIG. 1. The pharmacist then prepares thevarious dilution sets from the highest concentration maintenance dosageto the lowest concentration starter dose to provide sufficient dilutedpackaged doses of the respective doses for the complete program. It isimportant that all doses for the entire program from the lowest dose tothe highest dosage be provided from the batches. There will be more thanenough initial base concentration to provide the final diluted set ofpackaged doses. These base concentration vials can be reused multipletimes by the pharmacist. This is indicated by block 1110. This is thendispensed in a final form, as indicated by block 1112 in a final form atvarious dose levels. It may be that the packaging requires eachconcentration level to have a finite number of doses associatedtherewith and these doses can be provided in a single packaged dose orthey can be provided in separate packaged doses, each associated with asingle dose at that associated concentration level. Each of thesepackaged doses is sterile. That is, when they leave the compoundpharmacist, they will have a seal disposed thereover which, uponbreaking the seal, results in an unsterile environment. If each dose isa single packaged dose, the physician can be assured that the physicianor technician, when administering this dose, starts with a sterile dose.

This final form of dosages will be then delivered to the physician in anentire set, as indicated by block 1114.

Referring now to FIG. 12, there is illustrated a flowchart for theoperation of creating the dilution sets. This is initiated at a block1202 and then proceeds to a block 1204 to create the dilution sets. Thisis facilitated by providing six vials of a saline solution into which apredetermined amount of allergen at a defined concentration level can beintroduced. This is described in detail with respect to FIG. 1, above.By introducing a small amount of concentrated allergen or allergens frombase concentration vials into a first of the six vials, a first dilutionlevel, the highest, is achieved. This is mixed and then a small amountof this concentrated allergen or allergens is then introduced into thenext vial and so on until the last and sixth vial is created at thelowest and starter concentration level. These six vials require aninitial dilutant level sufficient to provide enough diluted allergen orallergens to provide a single or multiple therapeutic doses. Forexample, if a physician designed a program wherein the first dosagelevel required an introduction of ½ mL of diluted allergen or allergensfor a total of 10 doses over a first time period, that would requireonly 5 mL of total diluted allergen or allergens as an initial startingbase. However, it should be understood that, in order to obtain 5 mL ofdiluted allergen or allergens, there would have to be larger than a 5 mLbottle, since some diluted allergen is pulled from one bottle to thenext. Thus, typically, if 5 mL of diluted allergen or allergens wasrequired, a 10 mL bottle would typically be utilized. This, of course,is up to the compound pharmacist. In any event, at the first dosagelevel, the compound pharmacist would have to provide a sufficient amountof diluted allergen or allergens at that starter concentration level toprovide 10 doses. This operation is illustrated in block 1206. Once thesix vials at the increasing dilution levels from the starter dilutionlevel have been created, the diluted allergen or allergens for each ofthe sets is then transferred to a transdermal cream, as indicated by ablock 1208. The transdermal cream may also contain other medications,such as imiquimod, or the other medications may also be mixed in alongwith the diluted doses or at a later time. As noted hereinabove, eachdose will be defined as associated with a predetermined volume oftransdermal cream. Thus, the amount of transdermal cream for the totalnumber of doses required for a particular set will be defined and thatamount of allergen or allergens at that concentration level then will betransferred to the carrier transdermal cream. This will then be mixed,as indicated by block 1210, to ensure that the number of dosesintroduced to the carrier is thoroughly mixed throughout the carrier.This is then transferred to, for example, smaller dose containers,possibly one for each dose. This is indicated by a block 1212.

The final set of dose containers, there being a predetermined amount ofdoses for each concentration level, will be then shipped to thephysician, as indicated by a block 1214.

Referring now to FIG. 13, there is illustrated a diagrammatic view ofthe embodiment of FIG. 1, wherein there is added a second baseconcentration vial 103. This is indicative of at least two allergensbeing introduced into the program, it being understood that there couldbe more. The first and highest concentration or maintenanceconcentration vial 106 is first created with a small amount of allergenfrom each of the base concentration vials 103 and 102. If, for example,the vial 106 were a 10 mL vial, and the concentration level to beachieved in the vial 106 required there to be one half milliliter eachfrom vials 103 and 102, then the initial saline solution or the such(there can be multiple dilutant carriers) would have to be initially ata 9 mL level. Thereafter, the predetermined amount of diluted allergenswould have to be extracted from each vial in successive steps until thesixth vial 115. As noted hereinabove with respect to the embodiment ofFIG. 1, these concentration levels are defined from the initialconcentration level of the base allergen or allergens, and all that isdefined by the compound pharmacist is the amount or number of doses thatis required and the concentration level associated therewith. Typically,the concentration level for the starter dose in the vial 115 is definedby the physician and this defines what the higher concentration levelswill be, this being a traditional method.

The next step is to provide a plurality of containers 1302 having atransdermal carrier material. This is at a defined volumetric level suchthat a particular number of doses from each vial 106-115 can be disposedtherein. It may be that the physician only requires a certain number ofdoses for each set and these doses may be different. Thus, the compoundpharmacist may place only 10 doses in the container 1302 associated withthe vial 115 and 20 doses in the container 1302 associated with the vial106. Thus, the compound pharmacist must determine the amount oftransdermal cream associated therewith, assuming that each dose isassociated with a predetermined amount of transdermal cream. Thiscontainer 1302 could be sterilized and shipped to the physician in thatform, thus requiring the physician to then open the container, creatingan unsterile environment and then reuse it multiple times.Alternatively, the transdermal cream could be dispensed into smallersingle dose containers 1304 for each set. As noted in FIG. 13, there aresix final sets x′, y′, z′, a′, b′ and c′ for the respective vials106-115. Each of these sets can have a different number of dosesassociated therewith and, thus, a different number of small containers.These can be small round containers or these could even be tubes. Theobject is that each of these is sterilized, such that dispensing of asingle dose requires opening of the small container, resulting in anunsterile environment and an application of the transdermal creamtherein to administer a single dose. Thus, there is no reuse of theparticular container, resulting in the possibility of further bacterialcontamination of transdermal cream. With a single dose container, thetime between opening the container and use is short, thus minimizing thepossibility of bacterial contamination.

Referring now to FIG. 14, there is illustrated a flowchart for theoperation of creating the dilution sets. This is initiated at a block1402 and then proceeds to a block 1404 to create the dilution sets. Thisis facilitated by providing six vials of a saline solution into which apredetermined amount of allergen at a defined concentration level can beintroduced. This is described in detail with respect to FIG. 1, above.By introducing a small amount of concentrated allergen or allergens frombase concentration vials into a first of the six vials, a first dilutionlevel, the highest, is achieved. This is mixed and then a small amountof this concentrated allergen or allergens is then introduced into thenext vial and so on until the last and sixth vial is created at thelowest and starter concentration level. These six vials require aninitial dilutant level sufficient to provide enough diluted allergen orallergens to provide a single or multiple therapeutic doses. Forexample, if a physician designed a program wherein the first dosagelevel required an introduction of ½ mL of diluted allergen or allergensfor a total of 10 doses over a first time period, that would requireonly 5 mL of total diluted allergen or allergens as an initial startingbase. However, it should be understood that, in order to obtain 5 mL ofdiluted allergen or allergens, there would have to be larger than a 5 mLbottle, since some diluted allergen is pulled from one bottle to thenext. Thus, typically, if 5 mL of diluted allergen or allergens wasrequired, a 10 mL bottle would typically be utilized. This, of course,is up to the compound pharmacist. In any event, at the first dosagelevel, the compound pharmacist would have to provide a sufficient amountof diluted allergen or allergens at that starter concentration level toprovide 10 doses. This operation is illustrated in block 1406. Once thesix vials at the increasing dilution levels from the starter dilutionlevel have been created, the diluted allergen or allergens for each ofsets is then transferred to a vial, or to a transdermal cream, asindicated by a block 1408. As noted hereinabove, each dose will bedefined as associated with a predetermined administrable volume. Thus,the amount diluted antigen or antigens for the total number of dosesrequired for a particular set will be defined and that amount ofallergen or allergens at that concentration level. This is thentransferred to, for example, smaller dose containers, possibly one foreach dose. This is indicated by a block 1412.

The final set of dose containers, there being a predetermined amount ofdoses for each concentration level, will be then shipped to thephysician, as indicated by a block 1414.

Referring now to FIG. 15, there is illustrated a diagrammatic view ofthe embodiment of FIG. 1, wherein there is added a second baseconcentration vial 103. This is indicative of at least two allergensbeing introduced into the program, it being understood that there couldbe more. The first and highest concentration or maintenanceconcentration vial 106 is first created with a small amount of allergenfrom each of the base concentration vials 103 and 102. If, for example,the vial 106 were a 10 mL vial, and concentration level to be achievedin the vial 106 required there to be one half milliliter each from vials103 and 102, then the initial saline solution or the such (there can bemultiple dilutant carriers) would have to be initially at a 9 mL level.Thereafter, the predetermined amount of diluted allergens would have tobe extracted from each vial in successive steps until the sixth vial115. As noted hereinabove with respect to the embodiment of FIG. 1,these concentration levels are defined from the initial concentrationlevel of the base allergen or allergens, and all that is defined by thecompound pharmacist is the amount or number of doses that is requiredand the concentration level associated therewith. Typically, theconcentration level for the starter dose in the vial 115 is defined bythe physician and this defines what the higher concentration levels willbe, this being a traditional method.

The next step is to provide a plurality of containers 1502 for receivingthe proper amount of diluted antigen or antigens representing number ofdoses for a particular set. This is at a defined volumetric level suchthat a particular number of doses from each vial 106-115 can be disposedtherein. It may be that the physician only requires a certain number ofdoses for each set and these doses may be different. Thus, the compoundpharmacist may place only 10 doses in the container 1502 associated withthe vial 115 and 20 doses in the container 1502 associated with the vialsix. This container 1502 could be sterilized and shipped to thephysician in that form, thus requiring the physician to then open thecontainer, creating an unsterile environment and then reuse it multipletimes. Alternatively, the diluted antigen or antigens could be dispensedinto smaller single dose containers 1504 for each set. As noted in FIG.15, there are six final sets x′, y′, z′, a′, b′ and c′ for therespective vials 106-115. Each of these sets can have a different numberof doses associated therewith and, thus, a different number of smallsingle dose vials or containers. This small dose vial, compared to amultiple dose vial, allows dispensing of a single dose upon opening ofthe small vial, resulting in an unsterile environment once opened andupon application of a single dose. Thus, there is no reuse of theparticular vial, resulting in the possibility of further bacterialcontamination of the diluted antigen or antigens. With a single dosevial, the time between opening the vial and use is short, thusminimizing the possibility of bacterial contamination.

Referring now to FIG. 16, there is illustrated an overall therapeuticprocess flow for administering the therapeutic program to a particularpatient, with a particular and defined program that is tailoredspecifically to that particular patient. This, as described hereinabove,is result of the testing and the design of the program for thatparticular patient and the subsequent manufacture and supply of thedilution sets for that particular patient in accordance with the design.

Initially, there are provided a plurality of dilution sets, each of thesets associated with a particular concentration level. These are definedas dosage sets D1, D2, D3, D4, D5 and D6. This defines a completeprogram, noting that each dosage set can have a different number ofindividual dosages associated therewith. This is defined as the program1602. The physician then administers these in the following way. Thereis illustrated a timeline on the left side of the figure. The firstdosage set D1 is administered in the office. If there were, for example,a requirement that five single doses be introduced subcutaneously to thepatient at an interval of three days, that would require the patient tocome into the physician's office every three days for five visits. Inthis manner, the physician can evaluate the patient to determine ifthere is any adverse reaction. This will continue for a period of timeassociated with that first dosage set D1. Thereafter, the second dosageset D2 will be administered over a second time period as defined by thenumber of doses in the dosage set D2 and the interval over which theyneed to be administered. For example, this dosage set could have sixdoses applied every two days, requiring the patient to come in for sixvisits separated by two-day increments. This will continue until thelast dosage, D5 is to be applied in the office. At this point, thephysician administers this last dosage to the patient at the prescribedinterval for the number of doses associated with that particular dosageset. Once this has been completed, the last interval of time is entered,this being the maintenance interval. At this point, the last dosage setD6 is then packaged in a package 1610 and provided to the patient withinstructions such that the patient can administer these dosesthemselves. It could be that these doses are provided in a transdermalcream or they are provided with injectable vials. It could be that thereis provided a single vial with multiple doses with an indication thatonly a certain amount is to be utilized for each dose or there could bemultiple vials, each vial associated with a single dose to provide amore sterile environment overall.

Referring now to FIG. 17, there is illustrated a diagrammatic view ofthe overall system for transferring NDC's between systems. The NDC, orNational Drug Code, is a unique 10-digit, 3-segment number. It is auniversal product identifier for human drugs in the United States. Thecode is present on all nonprescription (OTC) and prescription medicationpackages and inserts in the U.S. The 3 segments of the NDC identify thelabeler, the product, and the commercial package size. The first set ofnumbers in the NDC identifies the labeler (manufacturer, repackager, ordistributor). The second set of numbers is the product code, whichidentifies the specific strength, dosage form (i.e, capsule, tablet,liquid) and formulation of a drug for a specific manufacturer. Finally,the third set is the package code, which identifies package sizes andtypes. The labeler code is assigned by the FDA, while the product andpackage code are assigned by the labeler.

For example, the NDC for a 100-count bottle of Prozac 20 mg is0777-3105-02. The first segment of numbers identifies the labeler. Inthis case, the labeler code “0777” is for Dista Products Company, thelabeler of Prozac. The second segment, the product code, identifies thespecific strength, dosage form (i.e, capsule, tablet, liquid) andformulation of a drug for a specific manufacturer. In our case, “3105”identifies that this dosage form is a capsule. The third segment is thepackage code, and it identifies package sizes and types. Our exampleshows that the package code “02” for this bottle of Prozac identifiesthat 100 capsules are in the bottle. The FDA maintains a searchabledatabase of all NDC codes on their website. This is illustrated in FIG.17A.

The NDC codes are unique codes that are applied for and assigned tospecific individuals to be associated with specific products. Eachmanufacturer of allergens, for example, has a unique NDC associated withthe product that they provide, which is assigned to that manufacture forthat product based upon their applying for such. The manufacturer,therefore, has full ownership of that NDC. In order for that NDC toappear in a database with the associated information the approval ofthat manufacture is required. For example, a manufacturer of awell-known drug will provide information to the database and populatethat database and the record associated with that NDC with theinformation regarding that product associated with that NDC but theywill also define what the AWP is for that product. It is themanufacturer, not the person that controls the NDC of the manufacturer,that controls what is in database, including the AWP. Additionally, itshould be noted that a distributor could actually apply for an NDC andcould populate or associate with that NDC information regarding aparticular product. They could actually place this NDC that they own,this being a unique NDC, in a database with another NDC, a different andunique NDC, that will be associated with basically the same product.This, of course, would provide some NDC contention within the databasewhich is to be avoided if possible.

Thus, a manufacturer 1702 has associated there with its own proprietarydatabase to store their NDCs. This can be provided to a central controlcenter 1706. The central control center 1706 desires to have access tothese NDCs of the manufacturer 1702. This is the primary reason thatthese NDC's do not exist in any other database. Typically, the centralcontrol center 1706 would have some type of contractual relationshipwith the manufacturer 1702 for the purpose of maintaining some type ofexclusivity with respect to the manufacturer's NDC. Thereafter, theseNDC's are stored in a central control database 1708. In this database1708, the central control 1706 can modify the information. Primarily,the main aspect that they had is the AWP. This allows the centralcontrol 1702 to control this AWP. There is, of course, the wholesalecost exactly charged for the product to an end user such as apharmacist, but the AWP is the benchmark price. This is not necessarilythe price that the pharmacist, for example, will charge to the customerbut, rather, it is the benchmark price. Further, this is not even theprice that will be reimbursed to the pharmacist even if the pharmacistbilled the customer for such. Thus, of course, this would not result inany type of price-fixing; rather, all that is controlled by the centralcontrol 1706 is the inclusion of AWP within the database. This AWP canbe utilized by the reimbursing entities and the such for centering on afinal reimbursement price.

In this disclosed embodiment, the data associated in with these venomderived allergens is then downloaded into a third party database 1710associated with a third-party information provider. This informationprovider is one of many information providers that provide accessthrough a network 1712 to a pharmacy 1714. It is noted, however, thatthe central control 1706 first confirms that none of the NDC'sassociated with any of the venom derived allergens is actually currentlyin the third party database 1710. Once these NDC's and their associatedinformation and associated AWP's are stored in the third party database1710, the central database 1708 has some control over both theinformation and the AWP associated with each of the NDCs. Thus, when apharmacist receives a request from a physician to fill a prescriptionfor a venom derived allergen for delivery to the physician, thepharmacist can access the third party database 1710 and determine thatthis is, in fact, in the database and is a reimbursable prescription.

Referring now to FIG. 18, there is illustrated a diagrammatic view ofthe third party database. This includes, in one column, NDC's, and asecond column AWP's and in a third column information regarding theproduct associated with the NDC.

Referring now to FIG. 19, there is illustrated a flowchart depicting theinitial operation of populating the database 1708. The central control1706 initiates the process at a block 1902 and proceeds to block 1904 inorder to receive the NDC from the manufacturer with the associatedinformation regarding the associated product. This is one associatedwith product in the database of the control center 1706 and also withproducts controlled by the control center 1706. The control center 1706is typically associated with some type of distribution center such that,in the information that they associate with the NDC in the database1708, the control center 1706 and the entity associated therewith arethe distribution arm for that product, i.e., this is where the productis ordered from by the pharmacist. The program then proceeds to a block1908 wherein the AWP for that particular product and associated withthat NDC is defined. This is a number that is set at whatever level isdetermined to be correct and appropriate by the control center 1706.There are a number of reasons for the price being set at any level.There is, of course, some cost of buying a product from the manufacturer1702, the markup and expenses associated with the operation of thecontrol center 1706, resulting in a wholesale price to the pharmacist.This wholesale price is not necessarily associated with the record thatis stored in the database 1710. However, it is this information that isutilized in determining what the AWP will be for that NDC and associatedproduct. A number of factors, of course, enter into that calculation,including practical knowledge of how the insurance industry reimbursesfor venom based allergens. After processing, the information is storedin the central control database 1708.

Referring now to FIG. 20, there is illustrated a flowchart depicting thetransfer of data, which is initiated at a block 2004 and then proceedsto a block 2006 to access the third-party database through the network1712. The program then flows to a function block 2010 to confirm that noNDCs in the control database 1708 exists within that third-partydatabase 1710. The program then flows to a function block 2012 topopulate the third-party database 1710 with information from the controldatabase 1708, which, as described above, includes the information fromthe manufacture, information regarding the central control center 1706as being a source of the product and the AWP for that product, allassociated with the NDC for that product. The program that flows to aterminate block 2014.

Referring now to FIG. 21, there is illustrated a flowchart for theoperation at the pharmacy. This is initiated at a block 2102 and thenproceeds to a block 2104 wherein the pharmacist receives a request froma physician for a venom derived allergen. This might actually bepresented to the pharmacist by a patient which desires to receive thevenom derived allergen for dilution and processing by the pharmacist orit may in fact be an already diluted venom derived allergen that couldbe actually self-administered by the patient. The program then flows toa decision block 2106 to determine if the product is in stock. If theproduct is in stock, the program flows to a function block 2112 to checkthe database for reimbursement and, if not, the program flows to a block2110 to process a stock item by whatever procedure the pharmacistutilizes. When checking the database, the pharmacist enters the NDC ofthe product, as indicated in a block 2114. The program then flows to adecision block to determine if the NDC is found, this being block 2116.If not found, the program exits and, if found, the program flows thefunction block 2118 wherein the pharmacist can view the AWP for thatproduct. This gives the pharmacist some idea as to what might bereimbursable, but also, the insurer itself will illustrate some type ofpotential co-pay. This just indicates the amount that the patient willpay at the counter. The pharmacist then can enter an amount that thepharmacist will claim that they want to be paid for this particularproduct. It may be less than the AWP but not more than AWP. This, ofcourse, is a function of what the pharmacist desires. This is indicatedby block 2120. Thus, there is provided a third-party database 1710having information contained therein, which is controlled by the centralcontrol center 1706 with respect to the venom derived allergens. Part ofthis is the AWP and part of it is the source for that venom derivedallergen. The insurer has access to this information and can utilize itto adjudicate a claim. Information from the insurer can be linked tothis database indicating a co-pay, for example. With respect to this,and insurer can indicate that it will pay the entire cost of theparticular venom derived allergen or indicate what percentage of thevenom derived allergen that it will pay for. Sometimes, it is just aco-pay. However, for some very expensive venom derived allergens, theinsurer may over time decide that it only pays a small percentage of thevenom derived allergen. This will be on an allergen-by-allergen basis.By allowing this third-party database 1710 to be controlled by thecentral control center 1706 with respect to the cost for the particularvenom derived allergen, this allows central control center 1706 tocontrol the adjudication of the particular venom derived allergen. TheProgram then flows to a function block to send a request to thethird-party payee for reimbursement, as indicated by block 2122.

The process for adjudicating any claim requires that some entity orparty has worked with the insurance company or the reimbursing entity tonegotiate the particular reimbursement or any benefits that areprovided. If the pharmacist is apprised of an AWP in the database for aparticular venom derived allergen, they at least have a price that theycan charge for the product. For example, if the pharmacist has a producton the shelf with an NDC any position writes a prescription for thatvenom derived allergen, the pharmacist just needs to know how much tocharge the patient. By accessing the third-party database 1710, the AWPcan be determined. However, that alone doesn't allow the pharmacist todetermine whether benefits are associated with that particular venomderived allergen. In order to do that, there has to be some link betweenan adjudicating party or entity. The pharmacist can select the NDC and afield (not shown) that directs the pharmacist to an adjudicating partyor entity to provide information as to benefits that are available. Ifsuch indicates that benefits are available, then the pharmacist knowsthat they can make a claim to this adjudicating party.

In the current disclosed embodiment, the central control center 106maintains the adjudicating database. The central control center 1706 isresponsible for interfacing with insurers and the such to provide thesebenefits. For example, if there are five major insurance companies thatreimburse the pharmacist or even Medicare, the central control center1706 will make the arrangements for reimbursement and allow thepharmacist to determine whether the patient, who may be associated withany of these reimbursement entities, can receive benefits. If, forexample, the patient had insurance with Insurer A, and central controlcenter 1706 had negotiated with Insurer A for certain benefits, thiswould be made available to the pharmacist. The benefits might providefor some type of co-pay which the pharmacist could charge to the patientand then the pharmacist could make a claim for the remaining value ofthe venom derived allergen to the adjudicating party, i.e., in this casethe central control center 1706. The central control center 1706 wouldthen process the claim and forward a check to the pharmacist. Since thecentral control center 1706 populated the third-party database 1710 withall of the NDCs, the central control center 1706 has exclusive rights toadjudicate these NDCs and the associated venom derived allergens. Thus,this unique link from the third-party database 1710 to the centralcontrol center 1706 allows all claims to be adjudicated therethroughbecause the central control center 1706 has exclusive control over theseNDC for these venom derived allergens.

All of the NDCs, as noted hereinabove, or for venom derived andallergens that are to be dispensed to a patient are a single dose venomderived allergen. Thus, each of the NDCs that would be obtained by themanufacturer would be for single dose venom derived allergens ratherthan bulk venom derived allergens that are currently provided.

FIG. 22 illustrates a flow chart depicting the operation wherein thecontrol center is able to determine the AWP by interfacing with thebenefit providers. This is initiated at a block 2202 and then proceedsto block 2204 wherein the control center assembles the various costinformation regarding the manufacturers cost to the control center, theexpenses of storing the venom derived allergen at the control center,i.e., where the control center is the distributor and provider of thevenom derived allergen, and what kind of markup or profit margin thecontrol center expects to receive on a venom derived allergen. Theprogram then flows a function block 2206 to determine the AWP. This AWPis based on the information retrieved in block 2204 and then a ceilingfor the AWP is determined. This ceiling is a number that is arrived atby the control center based upon their knowledge of how the benefitproviders reimburse pharmacists and the such. Since the AWP is a ceilingand the pharmacist cannot charge more than that, they provide a numberthat is a benchmark for the industry. By determining this benchmark, theinsurance industry will typically center in on a lower reimbursableprice, depending upon how valuable they think a particular venom derivedallergen or the such is to the industry. For example, if they sold theproduct for $350 to the pharmacist, this being the wholesale price, theymight set the AWP at $500. Over time, pharmacist may actually make aclaim for only $450 which, at first, the insurance copies may reimburse.After a time, the insurance industry may come to the conclusion thatthis venom derived allergen is only reimbursable at a rate of $400.

The program then flows to a function block 2212 wherein a control centercan interface with benefit providers to determine what the reimbursementlevels are and, if necessary, adjust the AWP. However, they can alsodetermine such things as rebate programs and incentives and the suchthat they can provide to the pharmacist, as indicated by a functionblock 2214. Since they control the database, they can also writeinformation from the interface with that particular part of thedatabase. The program then flows to a function block 2216 to adjust theAWP if necessary and then into a function block 2218 to adjust theinformation in the database if necessary.

The overall operation of initially testing patient at the physician'soffice, writing a script for the patient and completing the prescriptionby processing that script at a pharmacist location or some type ofcompounding pharmacy operation. In general, it must be noted that eachscript is very patient-specific; that is, in a system that is unique totesting for venom derived allergens, it is necessary to determine whichof multiple antigens must be combined in a desensitization program. Itmay be that, for example, a prick test initially indicates that thepatient is highly allergic to cat fur, dog care, various types ofpollen, certain venoms, and the such. With a positive indication forthese particular venom derived allergens, the physician can thendetermine which antigens need to be combined in some type of prescribeddosage regimen. Since there are so many venom derived allergens that canexist and since each patient is an individual, this combination can besomewhat daunting if the desire of the industry were to provide onlythat particular combination as a “drug” that has an NDC associated therewith. This is practically impossible, of course.

Referring now to FIG. 23, there is illustrated a flow diagram of theoverall process of determining a particular combination of antigens todesensitize an individual and the regimen therefore. This is initiatedat a block 2302 wherein the physician subjects the patient to what isknown as a “prick” test. This prick test is a test whereby the physicianintroduces a small amount of venom derived allergens into a small areaon the skin of an individual. There can be multiple spots that arearranged in a grid on, for example, a portion of the back of thepatient. These allergen locations are recorded and then they areobserved over a certain period of time. There is also typically sometype of base allergen that is provided such as a hypoallergenic antigenand a hyper allergenic antigen such that there is an area that willresult in no response and as an area that will result in a guaranteedresponse. Upon observation, areas that elicit a positive responseindicate that the patient is sensitive to that particular allergen. Itmay be that the patient is very sensitive to certain of the allergensand just mildly sensitive to others. The physician then determines whichof the allergens need to be included in a desensitization program. Forexample, if an individual in Texas showed a positive response to someallergen that rarely occurred in Texas, the physician might not includethat in a desensitization regimen.

Once the regimen is set upon for a particular patient, a script is thenwritten by the physician, as indicated by block 2304. This can be ascript for a single venom derived antigen if that was all that wasrequired for a desensitization program or it could be for a cocktail ofmultiple venom derived antigens. The physician will define the venomderived antigen or antigens that are to be included in the regimen, thedosage level and the carrier. For example, for the first desensitizationlevel, the most diluted level of antigen will be utilized. Typically,the physician will require that the single venom derived antigen orcocktail of antigens be provided in a carrier such as saline or glycerolin a vial that will allow for a certain number of injections. It may bethat the physician wants to prescribe for this first desensitizationlevel a dosage that will allow for three injections per week for threeweeks.

This script is then written and provided to the patient or it can bedirectly delivered to the pharmacist, as indicated by a path 2306 to ablock 2308 indicating the pharmacist. The pharmacist then creates apatient-specific venom derived antigen cocktail, as indicated by block2310. The pharmacist then lists the antigens that are contained withinthe cocktail, noting that there could be a single antigen. This isindicated at a block 2312 and then the pharmacist accesses the databasefor price and benefits. This is basically the Pharmacy Benefits Manager(PBM) database, which contains all of the drugs, etc., that areavailable for reimbursement. If the pharmacist, for example, looks up aparticular antigen that was prescribed in the script and does not findit, this indicates that it is not something that can be reimbursed. If,however, this antigen exists within the database, it indicates both theAWP for that antigen and benefits associated there with. All of this ispre-populated within the database. However, with respect specifically toany antigen, the NDC for that antigen will only be associated with thebase concentrate level. The script, however, is for a particular diluteddosage of that particular antigen and even a combination of multipleantigens at that particular dosage. This database is accessed at a block2314 and then, after access is complete, as indicated by a decisionblock 2316, the prescription is filled at a block 2318. The operation ofdetermining the particular AWP and benefits associated with any scriptfor antigens at any dosage level, wherein the particular combination ofantigens does not have particular NDC associated therewith nor does anyantigen by itself have a particular NDC associated therewith, it isnecessary to cross correlate this with an NDC that has an AWP associatedtherewith. Further, with respect to antigens specifically, the currentNDC for any antigen is associated with the base concentrated materialand this base concentrated material is too toxic to utilize at thatconcentration level. Thus, anything that is distributed to the patientwill always be diluted from this base concentrated material. As will bedescribed hereinbelow, it is always necessary to cross correlate anydosage level back to the NDC for the base concentrated material in orderto determine benefits. Further, each of the scripts set forth by thephysician will always have a list of each of the one or more allergensto which the patient exhibited a level of sensitivity thereto and theantigens associated there with. Further, the physician will determinethe dosage level also. This is indicated by block 2320.

Referring now to FIG. 24, there is illustrated a flowchart depicting theoperation of accessing the database, which is initiated at a block 2402and then proceeds to a decision block 2404. The decision block 2404determines whether a request for access has been received and, if so,the flowchart proceeds to a block 2406 to determine if the particularrequest of the PBM database is associated with that for an antigen. Ifnot, the program will follow the “N” path to a block 2402 to proceedalong the normal benefit determining process. This is not describedherein. If, however, the request is for an antigen, this is a specificoperation, since the only NDC that exists is for a base concentratedantigen that is too toxic to be directly distributed to a patient or foranother dosage level that is to be diluted. Once an antigen NDC asindicated, the program flows to a block 2410 in order to receive the NDCfor the base antigen or antigens and then to a block 2412 to receive thedose level for all of the antigens, as well as the carrier and thedilution procedure that is utilized. The program will then flow to ablock 2414 in order to cross reference the particular dose level thatwas actually distributed to the patient to the dose of the highestconcentrated level of the base concentrate material. This will be on aparsed operational level. This parsed operational level means that, forexample, if 10 antigens were distributed in a cocktail, it would benecessary to cross reference the distribution of this particular dosagelevel to the actual material utilized from the NDC-carrying baseconcentrated level. If, for example, for a single base concentratedmaterial that yielded an antigen in the cocktail mixed, required 1 mLout of a 50 mL bottle, the benefits for that one milliliter could bedetermined, as this is a “dosage” of the base concentrated level that isassociated with an NDC. As indicated by a block 2416, the benefits canbe determined for “each” allergen at a base or lowest concentrated levelthat is associated with an NDC. It is noted that an NDC might beprovided for an already diluted level of a particular antigen. However,it is always necessary to determine what portion of the NDC-carryingmaterial is utilized down to the final diluted level and then crosscorrelate this back to the NDC-carrying material at its particulardilutant level, this requiring some information as to the procedure fordilution, the carrier, etc. in order to adequately determine exactly howmuch of the NDC-carrying material was utilized. The program thenproceeds to a block 2418 to then access the benefits and then to a block2422 to end program.

Referring now to FIG. 25, there is illustrated a flowchart for theparsing operation, which is initiated at a block 2502. The program thenproceeds to a block 2504 in order to receive the prescribed scriptlevels. The program then proceeds to a block 2506 in order to parseantigens in the cocktail to individual antigens (noting that a singleantigen could be provided for). The program then flows to a block 2508in order to cross correlate each of the parsed antigens and the scriptdose level back to the base concentrated amount, noting that thisrequires the carrier to be known, the procedure to be known fordilution. Since the script merely states that the most diluted levelmust be provided for, the pharmacist then to provide that particularantigen. The particular base concentrated antigen could be at differentconcentrated levels which would require a pharmacist to utilize one ofmultiple dilution procedures to obtain the final diluted leveldesensitization regimen. However, as will be described hereinbelow, itcould be that physician prescribes a particular antigen in the cocktailthat can be found in an antigen at a base concentrated level thatcontains multiple antigens. This is very common in the industry. Forexample, some companies deliver already mixed cocktails for varioustypes of pollen. If the physician only prescribed one out of these typesof pollen, then this procedure must be noted so that particular amountof base concentrated material, that can be reimbursed based upon itsNDC, could be allocated. For example, if it were determined that 1.0 mLof the base concentrate pollen cocktail were required in order to getthe prescribed amount of the one type of pollen, and this was from a 50mL bottle, this would indicate a 1 mL dosage of the base concentratelevel, but this would be divided by the number of particular antigensthat are in the base concentrate material. If there were, for example,ten antigens contained in the cocktail, then this would be divided suchthat only 1/10^(th) of the dosage would be applied to benefits. That is,a 50 mL bottle would be considered as containing, assuming that thestarting dosage is always 1 mL or any deleting process, as having 500dosages of individual antigens. This, of course, requires knowledge ofthe dilution procedure, as indicated by a block 2510. Once thecrosscorrelation is complete, the program proceeds to a return block2514.

Referring now to FIG. 26, there is illustrated a flowchart depicting oneexample of the generation of a script for a single antigen and fillingof that fiction based on that script and getting reimbursed therefor.This is initiated at a block 2602 and then proceeds to a block 2604 inorder to prepare the physician script for a single antigen. The programthen flows to a block 2606 in order to define the requirements of themaximum dilution for the initial desensitization. The physician definedat which level the script is written for. For example, the physiciansets forth a regimen. This regimen defines six levels of dilution of adefined NDC base concentrate antigen, each level of dilution arerequired for a predetermined amount of time. For example, the mostdiluted level might be required to be administered in three doses perweek for three weeks for total of nine doses. The first script wouldrequire the pharmacist to deliver to the patient a vial containing ninedoses at that diluted level of the at least a single antigen. Thephysician could then require the second higher level to be provided overthe course of one week at three doses per week. This might require asecond script to be filled by the pharmacist or, alternatively, thepharmacist could fill that script that same time and maintained thatparticular vial on the shelf for distribution to the patient at a latertime, all of this depending upon the script provided by the physician.Of course, the physician could require the patient to come into theoffice for observation and then write another script. This would be aseparate and distinct operation and prescription which would beindependently associated with a different set of benefits possibly.

After the dilution level is determined for the initial desensitizationor at any level in the desensitization regimen, the program flows to afunction block 2608 wherein the pharmacist selects concentrate antigenand then goes to the dilution process required in order to achieve thedesired diluted level. The program then proceeds to a function block2610 wherein the pharmacist enters the NDC code for the base concentratelevel and the script level. Basically, what the pharmacist does is enterthe antigen name and the dosage level provided by script. The programthen proceeds to a function block 2612 in order to perform a lookup inthe PBM database for the particular antigen that is associated with thescript. This lookup does a correlation, as will be describedhereinbelow, to the lowest concentrate level having an NDC for thatparticular antigen. Knowing the dilution level and the procedure, it ispossible to determine what amount of the NDC-carrying concentrate levelfor that particular antigen was utilized and then a reimbursementobtained therefor. This is indicated by the function block 2614 and2616. The program then flows to an initial End block 2618.

Referring now to FIG. 27, there is illustrated a table for a singleantigen and the overall crosscorrelation information. This is arelational database. In this table can be seen that there is provided acolumn for the NDC code which is populated for a particular antigen.This indicates the name of the antigen and also information associatedthere with. There is also a dilution procedure for multiple proceduresthat can be associated with administering this particular antigen. Sincethe NDC code is not associated only with the type of antigen but alsothe concentration levels, this will be associated with the dilutionlevel to determine what the various dilutant levels are in the overallstandard process. As noted, the base level is indicated by a dilutantlevel D1 or a base concentrate level there than provide five additionaldilutant levels D2 through D6. Each one of these dilutant level columnshas associated there with a particular range of dilutant levels. Asindicated by example, there are levels 1 through 3 for each of dilutedlevels, with more possible. Therefore, if the most diluted level, D6were selected and that the procedure required that the dilutant level Z6for the dilutant level column D6 were selected as the end dilutant levelthat was required by the physician in the script provided to thepharmacist, this would be what was put into the PBM system. However,there is no NDC associated with this particular antigen at thisparticular dilutant level. Therefore there must be some crosscorrelationback to column D1 for the base concentrate level, which column has anNDC associated there with. If the final dilutant level was Z6, thiscould be cross correlated back within the same row to the dilutant levelZ1 of the base concentrate. However, although not shown, there couldactually be multiple rows associated with the dilutant level Z6, one foreach dilution procedure. Thus, the crosscorrelation from the antigen ata dilutant level back to the amount of bass constitute antigen requiredto process through the diluting procedure requires knowledge of thediluting procedure. This is illustrated in FIG. 27A, wherein each columnfor the dilutant level D6 has three procedures such that there areprovided three different amounts of the base extract that would berequired, Z1, Z1′ and Z1″. For example, it might be that this requirescorresponding levels of 0.8 mL, 1.0 mL or 1.1 mL for those threedifferent levels in order to accommodate the three different dilutionprocedures S1, S2 and S3. Thus, it is not just a mere crosscorrelationoperation but, rather, and overall knowledge of the process that isrequired in order to determine how much actual product was utilized ofthe original base NDC-carrying antigen. Only when the amount of the baseconcentrate NDC-carrying antigen that is utilized is known can theactual dosage be determined. For reimbursement purposes, it is importantto know whether 0.8 mL, 1.00 mL or 1.1 mL of the base concentrateNDC-carrying antigen is utilized. Reimbursement is calculated based uponthis. However, all that is necessary for the pharmacist to do is to putin the end product that was generated and the procedure for coming upwith that end product and relate that to the NDC of the antigen that wasutilized.

Referring now to FIG. 28, there is illustrated a flowchart for a secondexample for preparing a script for a cocktail, which is similar to theflowchart of FIG. 26. This is initiated at a block 2802 and thenproceeds to a block 2804 to generate a script for a cocktail which is apatient-specific cocktail based upon a prick test performed. This isunique to that patient for that particular time. The program thenproceeds to a function block 2806 in order to provide in that script alist of the antigens to be placed into the cocktail by the pharmacist,the final dilutant level of each, the dosage and the particular carrier.The program then flows to a function block 2808 in order to select theprocedure that the pharmacist will utilize to provide this final dilutedproduct with the prescribed number of dosages. This might be prescribedby the physician or it might be selected by the pharmacist. The programthen flows to a function block 2810 wherein the pharmacist performs thedilution operation and then combines various antigens into the cocktail,at a block 2812. The program then proceeds to a function block 2814wherein the NDC for each antigen is entered into the database, the doselevel and the procedure. The program then proceeds to a function block2816 to parse the particular antigens at the database, this parsingrequired in order to process each antigen in the database separately, asthere must be a crosscorrelation back to each individual antigen, sinceonly each individual antigen has an NDC associated there with. Theprogram then proceeds to a function block 2818 in order to correlate theantigen back to the lowest concentrate NDC-carrying level, as describedhereinabove with respect to the embodiment of FIGS. 26 and 27 and thento a function block 2820 in order to define the benefits and then to afunction block 2822 in order to end the program, after the cocktail hasbeen distributed to the end user such as the patient or the medicalprofessional.

Referring now to FIG. 29, there is illustrated a process, which issimilar to that described hereinabove, for creating a cocktail fromthree different base concentrate antigens 802, 804 and 806, referringhereinabove to the description with respect to FIG. 8. These are diluteddown in five separate steps to a final dilution level D6. In a firstoperation, there is provided a final vial 2902 that receives the finaldosage from each of the processes for diluting the initial baseconcentrate levels. It may be that each of the final vials D6 each have5 mL contained therein. By containing no carrier material in the finalvial 2902, 3 mL of each of the extracts can be placed therein resultingin a vial with 9 mL therein. If the physician prescribed the regimen todeliver a 1 mL dose of this concentrated level three times per week forthree weeks, this would require nine doses and thus 9 mL of thecocktail. This overall process, for example, would require thepharmacist to understand each step of the dilution process to arrive atthe final diluted. Thus, the pharmacist would indicate that there werethree antigens in the final vial 2902 and that they were at theconcentrate level D6/D6/D6. This would be provided to the PDM database.With this information alone, the system at the PDM database can crosscorrelate this back to the exact amount of base concentrate level liesfor each of three base concentrate antigens 802, 804 and 806 utilized.

Alternatively, there is provided a vial 2904 which is the result of adifferent selection of cocktails from the D4 level. This, again, wouldhave the three antigens in the concentrate level D4/D4/D4. This wouldagain be provided to the PDM database which would then, based upon thedilutant level for each of the antigens and the procedure utilized toachieve that dilutant level to relate this back to the antigens utilizedat the lowest NDC-carrying concentrate level. If, for example, this vial2904 resulted in 9 mL of material but the physician only required threedoses of 1 mL each for two weeks, this would only require 6.0 mL. Thepharmacist might only dispense 6 mL out of the 9 mL to the patient orprofessional. Even though three doses were distributed or 6.0 mL, this 6mL of final product of D4/D4/D4 of Cat/Dog/Pollen, for example, or avenom derived antigen, antigen has to be related back to the originalantigen value.

In an alternate embodiment, there is a vial 2906 provided that has beenprovided where in it receives diluted antigens from slightly differentvials. In this operation, the three antigens are D5/D6/D6 and this isprovided back to the PDM database. Of interest is that all three vials2902,2904 and 2906 will each be input to the PDM system with theirprocedure and the result will be that, for this example specifically,that the reimbursement be the same, as the starting dilutant will beidentical. This is procedure specific and script specific, with thecocktail noted as being patient-specific.

Referring now to FIG. 30, there is illustrated an alternate embodimentwherein each of the base antigens 802, 804 and 806 are subjected to adifferent procedure wherein each of the original starting amounts areinput to a first diluting vial 3002 and are subsequently diluted throughvials 3004,3006, 3008 and 3010 to a final vial 3012. This is thendistributed to the patient. This final vial represents the dilution atthe vial 3010, which is D6/D6/D6. This, along with this procedure, isthen transferred to the PDM database, as indicated by block 3020, whichis then parsed to the specific antigens and into a translator associatedwith each antigen, indicated by a “X” for the crosscorrelationoperation, blocks 3022, 3024 and 3026 associated with the Dog, Cat andPollen antigens, or venom derived antigens, which will then define thereimbursement. Each translation block 3022 will be associated with areimbursement database for defined benefits associated with theparticular antigen. Of course, it is important to know the amount ofantigen that was actually utilized in the overall procedure which,again, requires knowledge of the final script dilutant level of theantigen delivered to the patient and procedure for obtaining thatdiluted level.

Referring now to FIG. 31A, there is illustrated a diagrammatic view ofan overall process where in the NDC is associated with an intermediatelevel of dilutant. In this embodiment, the dilutant level D4 isillustrated as having an NDC associated there with, as well as the baseconcentrate level of Thus, it is possible that the reimbursement and bedefined back to this intermediate concentrate level. This is indicatedin a table in FIG. 31B, wherein the table can have associated withoriginal diluted levels D4, D5 and D6 crosscorrelation relationshipswith respect to the base concentrate level but, in this table, there areonly three diluted levels required, the dilutant level for vial D4, thevial D5 and the vial D6. If the concentrate level at the final vial wasX3 based upon the NDC code being at vial D4, all that would be requiredis to do a crosscorrelation back to the dilutant level required from thevial D4. This would be for each of the dilutant set was combined in avial 3102 from each of the antigens in the script, this indicated asbeing the antigens A1-N.

Referring now to FIG. 32, there is illustrated a process for mappingprick test to the script. As illustrated, there is provided a diagram ofthe prick test, indicated by a reference numeral 3202. This diagram 3202indicates the locations of the particular allergens that wereadministered to locales on the person of the patient. This diagramillustrates the results with a “P” indicating a positive reaction andthat an “X” indicating a negative reaction. Thus, the “P” indicates asensitivity that must be considered in the script. Of interest is thatthe particular manufacturers of antigens might have a cocktail alreadyexisting in the base concentrate. This is illustrated with the bottomthree test associated with antigens A(n−2), A(n−1) and AN. These are thelast three antigens in the list. Of these, the last two are positive andthe third for the last is negative. However, the script will have toinclude only the last two for the patient-specific script but thepharmacist only has the cocktail of all three available to them. Thus,the script will have a A0, A1, A3, A4 . . . , A(n−1) and AN as theantigens that are required for the desensitization regimen. This will beprovided to the pharmacist which will then select NDC-carrying antigenbottles A0, A1, A3, A4 . . . , And finally a bottle 3202 containingA(n−2), A(n−1) and AN, wherein only A(n−1) and AN are required in scriptto fill the prescription. This is then processed to provide the finalpatient dosage in the cocktail in the vial 3204.

Referring now to FIG. 33A, there is illustrated a flowchart depictingthe overall parsing operation before the operation of FIG. 32. In thisoperation, if the base NDC has a greater number of antigens than thescript, a decision block 3302 will determine such and flow to a block3304. The program will then flow to a function block 3306 in order todetermine the base dosage for the script as required by and set forth bythe physician of the antigens with the particular NDC, even though thatNDC is associated with more than the antigens required by the script.The program then flows to a function block 3308 in order to determinethe benefits. This is illustrated best with respect to the table of FIG.33B. Here, it is illustrated that there are three procedures forproviding the end dilutant level at the vial D6 for each of the antigensin the cocktail antigen vial 3204. If a certain amount of antigen isextracted from this particular vial 3204, it will contain all threeantigens. At a particular concentrate level at the level D6, this willyield the necessary concentrated level of the two antigens desired eventhough the third antigen is included. Since the final dilutant level isknown for the two prescribed antigens, they can be cross correlated backto the amount of antigen that was actually extracted. However, forexample, if 3 mL of the extract in vial 3204 were extracted, this mightrepresent a particular portion of a 100 mL bottle and, if all threeantigens have been prescribed, this would be the basis for thereimbursement. However, if only two antigens were prescribed, only twothirds of that prescribed extract would be reimbursed. Thus, byutilizing known script at the known dilutant level, this can be crosscorrelated back via the standard procedure (or whatever procedure isutilized) to what was actually utilized of the NDC-carrying baseconcentrate material to actually derive the final prescribed anddelivered antigen to the patient.

Referring now to FIG. 34A, there is illustrated a top view of oneembodiment of single dose antigen and imiquimod transdermal patch sheets3402 and 3404. In this embodiment, single dose antigen and imiquimodtransdermal patch sheets 3402 and 3404 each correspond to a differentantigen, A1 and A2, respectively, and each contain an amount ofimiquimod, in order to deliver a cocktail of imiquimod and antigens at aprescribed dilutant level. Additionally, single dose antigen andimiquimod transdermal patch sheets 3402 and 3404 may each correspond toa particular dilutant level for the antigen, such as dilutant level D6.Each of the single dose antigen transdermal patch sheets 3402 and 3404have a plurality of individual antigen specific single dose patches3406, with each of the plurality of patches 3406 having an antigencarrier 3408 and each patch constituting a “single” dose of theassociated antigen. The carrier 3408 may be a gel, such as a hydrogel, acream such as that described herein, or another suitable carrier for anantigen. The carrier 3408 may have already included a single dose at aparticular dilutant level of antigen, such as D6, or may only ship asthe carrier with no antigen included, so that the antigen can later beadded by someone such as a pharmacist. The carrier 3408 may also includea permeation enhancer. In the case of a hydrogel, the carrier may beproduced using ingredients such as polyvinyl alcohol, sodiumpolyacrylate, acrylate polymers, and copolymers. Each of the pluralityof patches 3406 may be cut from the sheet when a patch is needed.Antigen and imiquimod transdermal patch sheets 3402 and 3404 may thus beused for creating either single “single dose” antigen and imiquimodtransdermal patches, or a single dose patch made up of the combinationof antigens, such as both antigens A1 and A2, as will be describedherein.

Referring now to FIG. 34B, there is illustrated a cross sectional viewof one embodiment of a single dose antigen and imiquimod transdermalpatch 3410. The single dose antigen and imiquimod transdermal patch 3410may be one of the patches in the antigen transdermal patch sheets 3402and 3404 described in FIG. 34A. The single dose antigen and imiquimodtransdermal patch 3410 includes a back liner 3412. The back liner 3412may be made of a material that is impervious to an antigen carrier 3414,and any antigen therein, used in the patch. The patch 3410 furtherincludes a carrier platform 3416 upon which the antigen carrier 3414 isdisposed. Upon creation of the patch, the antigen carrier 3414 may havea single dose of antigen at a prescribed dilutant level alreadycontained within, or may later have an antigen added by someone such asa pharmacist for a single dose at a prescribed dilutant level. A firstadhesive coating 3418 adheres the carrier platform 3416 to the backliner 3412. The carrier platform 3416 may be of a circular shape and mayalso have a recessed middle portion forming a cell that allows for theantigen carrier to be held within. The patch 3410 further includes apharmaceutically diffusing cover 3420 that, when in use on a patient'sskin, allows for the antigen to pass through into the patient's skin.The cover 3420 may be made of a tissue material, silicone, or some otherporous material. The cover 3420 is held in place against the carrierplatform 3416 by a second adhesive coating 3422. A third adhesivecoating 3424 holds a peelable release liner 3426 over the cover 3420, toprotect the contents of the patch. Once the patch is to be used, thepeelable release liner 3426 is peeled away and the patch can then beapplied to the skin, with the adhesive coating 3422 serving to adherethe patch to the skin. It is noted that the amount of antigen andimiquimod disposed in the patch will be a sufficient amount that, whenreleased, will constitute a single dose “deliver” transdermally to thepatient and, thus, more than an actual single dose of antigen will bedisposed in the patch. The actual amount will vary depending upon thetype of patch and the delivery mechanism.

Referring now to FIGS. 35A-B, there is illustrated one embodiment of asingle dose multi-antigen and imiquimod patch 3500 at a particulardilutant level. The single dose multi-antigen and imiquimod patch 3500includes a backing 3502 upon which multiple single dose antigen andimiquimod patches 3504, such as those described in FIGS. 34A and 34B,and each having an antigen carrier 3506, may be adhered to, in order toprovide multiple single dose antigens in a single patch. The patches3504 each also include a peelable release liner 3508. The backing 3502may have designated spaces with adhesive coating for attaching each ofthe patches 3504, or the backs of the patches 3504 may have adhesiveapplied so they can be adhered to the backing 3502. In many embodiments,the patches 3504 are of a small enough scale that the single dosemulti-antigen patch 3500 need not be bigger than a standard transdermalpatch. The patch 3504 is identical to the patch described in FIG. 34B,except that they are attached to the backing 3502.

Referring now to FIGS. 35C-D, there is illustrated the single dosemulti-antigen (at a prescribed dilutant level) and imiquimod patch 3500in the process of preparation. This will hereinafter be referred to as a“multi-antigen” patch, it being understood that each antigen is a singledose at a prescribed dilutant level. The multi-antigen patch 3500 nowhas had each of the peelable release liners 3508 removed from thepatches 3504.

Referring now to FIGS. 35E-F, there is illustrated the multi-antigenpatch 3500 in the final stages of preparation. The multi-antigen patch3500 has had a new peelable release liner 3510 that covers the entiremulti-antigen patch 3500. The new peelable release liner 3510 may simplybe applied after removing all of the liners 3508 of the patches 3504 ifthe antigen carriers 3506 already contain a single dose of theassociated antigen. However, if the antigen carriers 3506 do not alreadycontain antigen, then, before the new peelable release liner 3510 isapplied, someone such as pharmacist may remove the covers 3420 of thepatches 3504 to add a single dose of antigen at a prescribed dilutantlevel to the antigen carriers 3506, replace the covers 3402, and thenadd the new peelable release liner 3510, noting that the terminology“add a single dose of antigen” is to be interpreted as adding asufficient amount of the associated antigen to facilitate “delivery” ofa single dose of antigen. A method of adding antigen to the antigencarriers is discussed hereinbelow.

Referring to FIG. 36, there is illustrated one embodiment of a processfor providing a single dose of antigen at a prescribed level in anantigen carrier. It will be understood that the carrier may also containimiquimod. There is provided a plurality of antigen patch sheets 3602,each having an antigen carrier cell 3604, the antigen carrier cellhaving a carrier such as a gel. The antigen patch sheets 3602 initiallyhave disposed thereon a liner strip 3606. The liner strip 3606 is peeledaway from the antigen patch sheets 3602, exposing the antigen carriercell 3604. An antigen 3603 is then injected into the antigen carriercell 3604. Once this is done, a peelable release liner 3608 is placedover the antigen patch sheets 3602, the peelable release liner 3608 alsoincluding a cover 3610 made of tissue, silicone, or some other porousmaterial. The peelable release liner 3608 is applied in such a way thatthe cover 3610 covers the antigen carrier cell 3604. In this way, eachof the antigen patch sheets 3602 may have a single dose of antigen at aprescribed dilutant level applied to each of the cells 3604 of thatparticular patch sheet. The antigen patch sheets 3602 may then be cut,in order to apply the antigen patches to a multi-antigen patch, such asthat shown in FIGS. 35A-F.

Referring now to FIG. 37A, there is illustrated one embodiment of amulti-antigen patch 3700. Multi-antigen patch 3700 includes a well 3702disposed on a base 3704. The well 3702 is of a circular shape havingrecessed portions 3706 separated by raised cross portions 3708. Therecessed portions 3706 contain a carrier gel 3707. While four recessedportions 3706 are illustrated in FIG. 37A, any number may be used.

Referring now to FIG. 37B, there is illustrated a cross-sectional viewof the multi-antigen patch 3700. The multi-antigen patch 3700 hasinitially thereon a liner 3710 covering the base 3704 and the well 3702,in order to protect the carrier gel 3707 during activities such asshipping.

Referring now to FIG. 37C, there is illustrated another cross-sectionalview of the multi-antigen patch 3700 after the liner 3710 is removed.Once the liner 3710 is removed, a single dose of antigen at a prescribeddilutant level, or multiple antigens at a prescribed dilutant level, maybe inserted into the carrier gel 3707 of the recessed portions 3706 ofthe well 3702. This is shown in FIG. 37C where, with the liner 3710removed, antigen A1 is inserted into the carrier gel 3707 of one of therecessed portions 3706 and antigen A2 is inserted into the carrier gel3707 of another one of the recessed portions 3706. In this way, thecarrier gel 3707 in each of the recessed portions 3706 of the well 3702would then carry the desired amount of antigen.

Referring now to FIG. 37D-E, there is illustrated a cross-sectional viewof applying a peelable release liner 3712 to the multi-antigen patch3700. The peelable release liner 3712 has spaced apart thereon covers3714, one for each recessed portion 3706. When the peelable releaseliner 3712 is placed onto the multi-antigen patch 3700, each of thecovers 3714 are inserted into or over a recessed portion 3706. Thecovers 3714 may be made of tissue, silicone, or some other material thatallows for the antigen disposed within the gel 3707 to pass through thecovers 3714 in order to come into contact with human skin. When themulti-antigen patch 3700 is to be used, the peelable release liner 3712is removed and the covers 3714 are placed against the skin. It will beunderstood that, as described herein, the multi-antigen patch 3700 maybe held in place on a patient's skin by an adhesive or some other means.

Referring now to FIG. 38, there is illustrated one embodiment of amulti-antigen patch antigen selection operation 3800. There isillustrated a custom patient-specific antigen results table 3802resulting from the prick test. The table 3802 has a plurality of allergyindicators 3804, each having an allergy associated with each indicatorhaving the letter “P” or “X,” with “P” indicating a positive allergyresult and “X” indicating a negative allergy result. This is used by thephysician to create the script for the patient to create thepatient-specific script. The results, when viewed by the medicalpractitioner, indicate the specific allergy reaction. For instance, theresults may show that a patient is allergic to cat dander and certaintypes of pollen. Each of these would be marked with a “P” on the resultstable 3802, with an “X” marking the other allergies having a negativeresult. From the results table 3802, the proper antigens needed for thepatient may be selected, the script generated, sent to the compoundingpharmacist and applied to a multi-antigen patch 3806. If the patient isallergic to allergens A₀ through A_(n), (reference number 3808), thoseallergens may be selected. Additionally, if certain antigens arecommonly distributed as part of one antigen compound, such as a cocktailof pollen antigens, those may be applied to a single patch. This issimilar to one bottle or dose of an antigen cocktail, as describedherein, except provided in a patch. For example, and as illustrated inFIG. 38 (reference number 3808), if antigens A₃, A₄, and A₇, aretypically be supplied together in the same antigen cocktail, then themulti-antigen patch 3806 may have antigens A₃, A₄, and A₇ within asingle antigen carrier 3810.

Referring now to FIG. 39A, there is illustrated a cross-sectional viewof one embodiment of a multi-antigen patch 3900. Multi-antigen patch3900 includes wells 3902 disposed on a base 3904. The wells 3902 are ofa circular shape having recessed portions containing a carrier gel 3907.Any number of wells may be present on a patch. The multi-antigen patch3900 may initially have thereon a liner 3910 in order to protect thecarrier gel 3907 during activities such as shipping.

Referring now to FIG. 39B, there is illustrated a top view of themulti-antigen patch 3900. As stated, the multi-antigen patch 3900 hasinitially thereon a liner 3910 covering the base 3904 and the wells3902, in order to protect the carrier gel 3907 during activities such asshipping.

Referring now to FIG. 39C, there is illustrated another top view of themulti-antigen patch 3900 after the liner 3910 is removed. Once the liner3910 is removed, a single dose of antigen at a prescribed dilutantlevel, or multiple antigens at a prescribed dilutant level, may beinserted into the carrier gel 3907 in the wells 3902. This is shown inFIG. 39C where, with the liner 3910 removed, antigen A1 is inserted intothe carrier gel 3907 of one of the recessed wells 3902, antigen A2 isinserted into the carrier gel 3907 of another one of the wells 3902, andantigen A3 is inserted into the carrier gel 3907 of another one of thewells 3902. This process may be repeated for each well 3702 disposed onthe multi-antigen patch 3900. In this way, the carrier gel 3907 in eachof wells 3902 would then carry the desired amount of antigen.

Referring now to FIG. 39D-E, there is illustrated a cross-sectional viewof applying a peelable release liner 3912 to the multi-antigen patch3900. The peelable release liner 3912 has spaced apart thereon covers3914, one for each well 3902. When the peelable release liner 3912 isplaced onto the multi-antigen patch 3900, each of the covers 3914 isinserted into or over an associated well 3902. The covers 3914 may bemade of tissue, silicone, or some other material that allows for theantigen disposed within the gel 3907 to pass through the covers 3914 inorder to come into contact with human skin. When the multi-antigen patch3900 is to be used, the peelable release liner 3912 is removed and thecovers 3914 are placed against the skin. It will be understood that, asdescribed herein, the multi-antigen patch 3900 may be held in place on apatient's skin by an adhesive or some other means. This thus allows fora single dose of each antigen that is included on the patch to betransdermally delivered. Further, once the patch is created, then thepharmacist need only provide the script and the antigen base concentrateNDCs utilized, the dilution procedure and the carrier to the PBMdatabase in order to determine the available benefits, as described indetail hereinabove.

It will be understood by one skilled in the art that variations made bemade to the patch without deviating from the present inventive concept.For instance, the patch may be a single-layer drug-in-adhesive, havingthe drug within the adhesive layer, a multi-layer drug-in-adhesive, amatrix system patch, or rate controlled membrane patch.

It will be appreciated by those skilled in the art having the benefit ofthis disclosure that this method provides a customized delivery ofallergen based on individual patient treatment plan. It should beunderstood that the drawings and detailed description herein are to beregarded in an illustrative rather than a restrictive manner, and arenot intended to be limiting to the particular forms and examplesdisclosed. On the contrary, included are any further modifications,changes, rearrangements, substitutions, alternatives, design choices,and embodiments apparent to those of ordinary skill in the art, withoutdeparting from the spirit and scope hereof, as defined by the followingclaims. Thus, it is intended that the following claims be interpreted toembrace all such further modifications, changes, rearrangements,substitutions, alternatives, design choices, and embodiments.

What is claimed is:
 1. A method for creating a consolidated compound fordelivering an immunomodulator and imiquimod to a patient, comprising thesteps of: providing a plurality of containers of concentratedimmunomodulator extract; for each container of concentratedimmunomodulator extract, diluting the immunomodulator extract with apredetermined dilutant in an associated sterile container approved forsuch dilution and to a desired dilution by transferring a quantity ofthe concentrated immunomodulator to the associated sterile container,the associated sterile container having a defined volume of dilutedimmunomodulator after dilution thereof, such that there is an associatedsterile container for each container of concentrated immunomodulatorextract; providing a viscous encapsulation material that is able tocarry immunomodulators across the dermis of the skin of a patient andhaving a defined volume disposed within a container, the defined volumedivided into a plurality of dispensable increments; selecting aprescribed amount from each of the sterile containers associated witheach of the containers of concentrated immunomodulator, the prescribedamount for each of the sterile containers defined as that amount of thediluted immunomodulator extract required to provide a number of dosesequal to a number of the plurality of dispensable increments from thecontainer containing the viscous encapsulation material, a doseproviding a desired therapeutic effect to a patient for each of thediluted immunomodulator extracts; and introducing an amount of imiquimodinto the viscous encapsulation material.
 2. The method of claim 1,further comprising: introducing the selected prescribed amount from eachof the sterile containers into the viscous encapsulation material. 3.The method of claim 2, further comprising: mixing the introduced amountof each of the diluted immunomodulator extracts and the introducedamount of imiquimod with the viscous encapsulating material.
 4. Themethod of claim 1, wherein introducing the amount of imiquimod into theviscous encapsulation material includes injecting the amount ofimiquimod into the viscous encapsulation material.
 5. The method ofclaim 4, further comprising: mixing the introduced amount of imiquimodwith the viscous encapsulating material to create a transdermalimiquimod cream.
 6. The method of claim 5, further comprising:introducing the selected prescribed amount from each of the sterilecontainers into the transdermal imiquimod cream; and mixing theintroduced amount of each of the diluted immunomodulator extracts withthe transdermal imiquimod cream.
 7. The method of claim 6, wherein thetransdermal imiquimod cream is configured to, when applied to thestratum corneum of the patient, cross the dermis of the patient tosubcutaneously deliver the immunomodulators.
 8. The method of claim 6,wherein the step of diluting comprises the steps of: providing aplurality of sterile containers, each associated with a differentdilution level; associated with each container of concentratedimmunomodulator extract, extracting a defined amount of concentratedimmunomodulator extract from the container of immunomodulator extractand disposing it within a first one of the associated sterile containerscontaining a dilutant to provide a first dilution level; extracting adefined amount of the diluted immunomodulator extract from the first ofthe associated sterile containers and disposing it within a second ofthe associated sterile containers to provide a second dilution level;and progressively extracting a defined amount of diluted immunomodulatorextract from a previous one of the associated sterile containers to thenext thereof containing a dilutant to provide progressively more dilutedlevels until the last of the associated sterile containers containing afinal dilution level.
 9. The method of claim 6, further comprising:disposing the transdermal imiquimod cream in one or more wells of atransdermal patch.
 10. The method of claim 1, wherein the step ofdiluting comprises the steps of: providing a plurality of sterilecontainers, each associated with a different dilution level; associatedwith each container of concentrated immunomodulator extract, extractinga defined amount of concentrated immunomodulator extract from thecontainer of immunomodulator extract and disposing it within a first oneof the associated sterile containers containing a dilutant to provide afirst dilution level; extracting a defined amount of the dilutedimmunomodulator extract from the first one of the associated sterilecontainers and disposing it within a second one of the associatedsterile containers to provide a second dilution level; and progressivelyextracting a defined amount of diluted immunomodulator extract from aprevious one of the associated sterile containers to the next thereofcontaining a dilutant to provide progressively more diluted levels untilthe last of the associated sterile containers containing a finaldilution level.
 11. The method of claim 1, wherein the immunomodulatorsinclude an antigen or an allergen.
 12. The method of claim 1, whereinthe viscous encapsulation material includes a transdermal cream.
 13. Atransdermal cream comprising: a viscous encapsulation materialconfigured to carry immunomodulators across the dermis of the skin of apatient, the viscous encapsulation material including: a prescribedamount of one or more diluted immunomodulators; and an amount ofimiquimod.
 14. The transdermal cream of claim 13, wherein the amount ofimiquimod is within a range of 0.5% to 9% by weight.
 15. The transdermalcream of claim 13, wherein the amount of imiquimod is 250 milligrams.16. The transdermal cream of claim 13, wherein the one or more dilutedimmunomodulators each include an antigen or an allergen.
 17. Thetransdermal cream of claim 13, wherein the transdermal cream is disposedwithin a container configured to dispense a prescribed amount of thetransdermal cream.
 18. The transdermal cream of claim 13, wherein thetransdermal cream is disposed in a transdermal patch.
 19. Thetransdermal cream of claim 18, wherein the transdermal patch includes: asubstrate; one or more wells having a rim portion protruding above asurface of the substrate and an interior portion lower than the rimportion; and an inner portion of each of the one or more wells, whereinthe transdermal cream is disposed within the inner portion of at leastone of the one or more wells.
 20. The transdermal cream of claim 19,wherein the transdermal patch further includes: an adhesive formed on asurface of the substrate outside a perimeter of the one or more wells;and a releasable film disposed over the substrate and the one or morewells.